CHEMOTHERAPY REGIMENS

.. A .. B .. C .. D .. E
.. F .. G .. H .. I .. J
.. K .. L .. M .. N .. O
.. P .. Q .. R .. S .. T
.. U .. V .. W .. Y .. Z

 

A

Adrenal
Anal

B

Bladder

Brain

Breast

C

Carcinoid

Cholangiocarcinoma

Colon (Adjuvant, Metastatic, in Renal Failure)

E

Endometrial

Esophagus

G

Gastric

H

Head and Neck

Hepatocellular

Hodgkin’s

L

Liver

Lung (Non-small cell, Small cell)

Lymphoma (Hodgkin’s, Low-grade, Aggressive, High Grade, Salvage)

M

Melanoma (Adjuvant, Metastatic)

Neoplastic meningitis

Mesothelioma

Multiple Sclerosis

Myeloma

O

Ovarian

P

Pancreas (Adenocarcinoma, Islet Cell)

Prostate (Metastatic, Low PSA)

R

Rectal (Adjuvant, Neoadjuvant)

Renal

S

Sarcoma

T

Testicular

U

Unknown Primary

 

 

ADRENAL: METASTATIC

FAP

5FU  500mg/m2        IV/1hr d1,2,3
DOX 60mg/m2          IVB      d2
CDDP 120mg/m2     IV        d2
--Cycle q 4 weeks
--23% RR, PR=6-12 months
--Cancer 67:2997 6/91

CDDP/VP-16

CDDP 25mg/m2       IV d1,2,3
VP16 100mg/m2       IV d1,2,3
--Cycle ?
--46% PR
--Proc ASCO 12:188 (Abs#544) 93

 

BLADDER (Neoadjuvant, Adjuvant, Metastatic)

Bladder: Adjuvant

Ifosfamide 2 gm/m2 IV/3 hrs days 1,2,3,4
Mesna 400 mg/m2 IV just before ifosfamide, just after, and at 3, 6, and 9 hours (5 doses total)
Doxorubicin 20 mg/m2 IV/18 hours days 1,2,3 after Ifosfamide
Gemcitabine 200 mg/m2 IV/30 min days 2,4 after last dose of Mesna
G-CSF days 7-12
Repeat q 3 weeks x 4-5 cycles. Doses had to be reduced by 20% in a number of patients.

Ref: Cancer 92:194, 2001, Millikan et al [MDACC]

 

Bladder: Metastatic

GEMCITABINE/CISPLATIN
(JCO 18:3068, Sep '00)

Gem 1000 mg/m2 IV/30 min d 1,8,15
CDDP 70 mg/m2 day 2
Given every 4 weeks

Hold gemcitabine on day 8 or 15 if WBC < 2 or platelet < 100. (Held doses are not made up, so a cycle could be 3 weeks instead of 4.)

RR = 49%
GP equal to MVAC, but less toxic. This can also be used in neoadjuvant setting.

TAXOL/CARBOPLATIN
(JCO 16:1844, '98)

Taxol 200 mg/m2 IV
Carbo AUC=5
Given q 3 weeks

RR 51%
Time to relapse = 6 months

CTX/GEM (MDACC)

Cytoxan        300 mg/m2 d 1,8
Gemcitabine  800 mg/m2 d 1,8
Given q 3 wks
or give biweekly instead of d1,8 if not tolerated well

BCG

BCG 81 mg intravesical q 1wk x 6 (induction)

MVAC (Yagoda 10/84)

MTX             30mg/m2 iv d1,15,22
VLB              3mg/m2 iv d2,15,22
DOX             30mg/m2 iv d2
CDDP           70mg/m2 iv d2

RR = 70% (30-40% CR) MS = 13mon

CMV

MTX 30 mg/m2 d1,8            
VLB  4 mg/m2 d1,8
CDDP100 mg/m2 IV/4h d1 (at least 12h after MTX)
Repeat q 3wk

RR = 42% in 62 patients w 26% cure rate.
JCO 3:1463 1985 

BLADDER: NEOADJUVANT

TMP (MDACC uses this)

Taxol 100 mg/m2 iv/1hr
Methotrexate 30 mg/m2 iv
CDDP 40 mg/m2 iv

Repeat weekly x 2 every 3 weeks (2 on/1 off) for 5 cycles.

Can also use regimens used in metastatic disease (see).

 

SELECTIVE BLADDER PRESERVATION BY COMBINATION TREAMENT OF INVASIVE BLADDER CANCER. NEJM NOV 1993

53 Patients with (T2-T4 NXMO) disease.

TURB-->Chemotx - 2 cycles MCV--> Cisplatin with 4000 cGy --> Re-evauate urologically -->
If PR --> Radical cyst-X
If CR --> Consolidate with Cisplatin + 2480cGy

Chemotx:

MTX 30mg/m2 iv D 0,14,21 & 28
Cisplatin 70mg/m2 D1
Vinblastine 3mg/m2 D 1,14 & 21

*Doses of MTX & PLAT decreased if serum cr > 1.5.

The rate of CR was 58% of 53pts but 68% of the 40pts who did not have tumor-associated hydronephrosis at presentation. Patients with hydronephrosis should not be treated with this method but with cystectomy.

 

BRAIN: HIGH GRADE GLIOMAS

Combination

PCV (Int J Rad Onc Biol Phys 18:321 1990)

CCNU 110 mg/m2 po d1
Procarb 60 mg/m2 po d8-21
VCR 1.4 mg/m2 IV d8, 29
Repeat q6-8wk

Procarb = 50mg caps. Divide number of caps to be taken over 14 days, with more towards end, not front. Take at bedtime.

CCNU = 40mg caps

Premed with po Kytril or Zofran for CCNU & Procarbazine as follows:
- Day 1: Zofran 8mg before CCNU and 6hr later
- Day 8-21: Zofran 8mg: 1/2 tab prior to procarb days 8-10.

Check counts q 2 wks

Avoid tyramine, alcohol, chocolate, & other drugs (look up)

RR = 26% in 46 patients. MTP = 6 mon.

 

Single Agent

BCNU 80 mg/m2 d1-3, q 8wk OR (J Neurosurg 49:333,'79)
          200 mg/m2 d1 q 8wk

CCNU  130 mg/m2 PO q 6-8wk

Procarbazine 50 mg/m2 TID d1-28, q8wk (Ca Treat Rep 67:121, '83)

RRs for single agents = 20-40%

----------------------------------------

PROC                                                             

Procarb 50 mg/m2 TID PO d1-28

Value of adj chemo limited & controversial. No single agent better than BCNU. Lit supports use of BCNU or combo of CCNU, procarbazine, and VCR. With multimodality therapy, 10-20% may live for 2yr or more.

Overall mean survival time for combined modality therapy is 40-50 wks, compared w 35 wks after surgery+RT. Depends upon histology of tumor being studied.

At recurrence, patients not previously treated w nitrosoureas respond to BCNU, CCNU, or combo of CCNU/procarbazine/VCR. Procarbazine may --> response in those previously txd w nitrosoureas. These strategies result in small but real survival benefits.

Of the combos studied in adj setting, that of lomustine (CCNU), procarbazine, and VCR (PCV) has been reported to be superior in txing anaplastic gliomas, producing a MS of 3yrs compared with 1.5yr for BCNU (carmustine).

For glioblastoma multiforme, PCV appeared better than carmustine (BCNU), altho inc survival was not sig.

 

CARCINOID & ISLET CELL TUMORS: METASTATIC

Streptozocin (SZN)+DOX has been shown to be superior to SZN+5FU in comparative trials, and both are better than SZN alone.

Agent                    RR%       
SZN                        45
DOX                       20
DTIC                       9
SZN+5FU              63
SZN+DOX             69
SZN+5FU+DOX    40

Regimen to use (SD):

SD

Streptozocin  500 mg/m2 IV d1-5
DOX 50 mg/m2 IV d1, 22
Repeat q 6 wks

FS Others (Holland) like better than SD:

SZN  500 mg/m2 IV d1-5    
5FU  500 mg/m2 IV d1-5
Repeat q 28d

Octreotide (Sandostatin)

Start 50mcg SQ BID, titrate up to 100mcg TID
Alternate: Start 100mcg SQ QID and titrate downward.

 

CHOLANGIOCARCINOMA - CHEMO

Gemcitabine 1000 mg/m2 d 1,8
Xeloda 1750 mg/m2 d 1-14
Repeat q 3 wks.

 

COLON CA - ADJUVANT DATA (regimens)

                   5FU/Lev None

3Y DFS           63        47
3Y OS             71        55

Can --> reversible rises in alk phos in 40%, and less common rise in AST, TB, or even CEA. Can confuse issue of recurrence.

(Moertel...NEJM 322:352, 1990)

--------------------------

DATA

Adjuvant therapy for Dukes C with 5FU/Levam has reduced recurrence by 41% in 3 large trials, improving survival 50-->62% and reducing death by 33%. (Not clear however whether this is truly better cure rate or delayed recurrence and death.)

Adjuvant 5FU+Levam in Stage II (B2) Colon Ca (JCO 13:2936 12/95). Reduced rate of recurrence by 38%, but no difference in survival. Had higher death rate on treatment arm due to non-cancer causes. May be that no effect shown bec harder to demonstrate benefit when 5YS from surgery alone is already 80%. Also, salvage surgery with curative intent may have resulted in lower death rate in control arm than otherwise might have been seen. In this respect, could say that one benefit of adjuvant therapy would be dec risk of needing surgery, but if needed, seems to work ok. Conclusion: decision to tx a personal preference. May decide to if poor prognostic features (adherence or invasion of adjacent organs, mesenteric implants, perforation, obstruction, aneuploidy, 18q [DCC] deletions).

High dose LV/5FU x 5 days/month vs obs in patients w Dukes B/C:      3YS 78-->83% overall and 64-->76% in Dukes C. These results comparable to standard 5FU/Levam weekly x 1 yr.          (IMPACT meta-trial, 1526 patients: Lancet 345:939, 4/95)

Comparison of obs/Levam only/ 5FU+Levam in patients w Stage III:

5FU+Levam reduced recurrence by 40% and death by 33%. Levam alone-no benefit. (Moertel, AIM 122:321, 3/95)

In rectal cancer, best results come w 5FU CIV+post-op XRT. HDLV and LDLV equivalent. Semustine adds little.
(Moertel [review] NEJM 330:1136, 4/94)

 

3-Yr DFS & OS According to Tx

--------------------------------------

DFS%               OS%

MOF LV+FU MOF LV+FU

--------------------------------------

Duke's B 82 87 93 95
Duke's C 58 67 71 79
1-4 LN 64 75 77 86
5+ LN 40 45 57 64

 

COLON CA – ADJUVANT THERAPY (data)

In stage C:
- decrease risk of recurrence by 41%
- decrease overall death rate by 33%
- 3.5 yr survival: 71%

5FU/HDLV

LV 500 mg/m2 IV/2hr
5FU 500 mg/m2 IV at 2 hrs

Give weekly x 6 months.
(Hancock gives it 3 wks out of 4 for 6 months.)

5FU/LDLV

LV 25 mg/m2
5FU 370 mg/m2
Give weekly x 30 wks.

The above 2 regimens are equally effective (Annals Onc 11:915, 8/00)

XELODA

1250 BID x 14d  every 21d  x 6 months (8 cycles)

FU/HDLV
(Proc ASCO #486, 1996)

LV 500 mg/m2 IV/2 hrs
5FU 500 mg/m2 IVP @ 1 hr
Give weekly x 6. Repeat q 8wk x 4.

Same results as Mayo regimen.

FU/LDLV
(Mayo)

(ECOG+SWOG+CALGB)

5-FU 425mg/m2 IV QD x 5, wks 1,5,9,14,19,24 (4w,4w,5w,5w,5w)
LV    20mg/m2 IV

In intergroup trial was as effective as 5FU/LEV x 1 yr (Proc ASCO #486 5/96)

 

COLON: METASTATIC

FOLFOX4, FOLFOX6, FOLFIRI, Avastin (Bevacizumab), ILF, FOLFOX, Weekly 5FU/LV, Irinotecan, Infusion 5FU, Mitomycin

FOLFOX4

Oxaliplatin 85 mg/m2 IV/2 hours, day 1
Leucovorin 400 mg/m2 IV/2 hours given same time as oxaliplatin, days 1 and 2
5FU 400 mg/m2 IV bolus, then 600 mg/m2 CIV over 22 hours, then repeat bolus at end of infusion after second LV dose
Repeat every 2 weeks

FOLFOX6

Oxaliplatin 85-100 mg/m2 IV over 2 hours, day 1
Leucovorin 400 mg/m2 IV over 2 hours, day 1 (give with oxaliplatin)
5FU 400 mg/m2 IV bolus, then 2400-3000 mg/m2 CIV over 46 hours
Repeat every 2 weeks

Modified FOLFOX7

Oxaliplatin 100 mg/m2 IV over 2 hours
Leucovorin 400 mg/m2 IV over 2 hours
5FU 3000 mg/m2 IV over 46 hours
Repeat every 2 weeks x 6

FUFOX

Oxaliplatin 60mg/n2 IV over 2 hours
Leucovorin 500 mg/m2 IV over 2 hours
5FU 2600 mg/m2 IV over 24 hours
Give weekly x 4 on a 6 week cycle

FOLFIRI

Irinotecan 180 mg/m2 IV over 90 minutes, day 1
Leucovorin 400 mg/m2 IV over 2 hours, day 1 (may give with irinotecan via Y-connector)
5FU 400 mg/m2 IV bolus, then 2400-3000 mg/m2 CIV over 46 hours
Repeat every 2 weeks

XELOX

Xeloda 1000 mg/m2 BID days 1-14
Oxaliplatin 130 mg/m2 day 1
Repeat every 3 weeks

Bevacizumab (Avastin)

May give with the above regimens.
Give before 5FU bolus/infusion.
Dose: 5 mg/kg IV every 2 weeks.

ILF - Douillard

(Douillard Regimen, Lancet 355 3/00) – may have less risk for life-threatening complications than the Saltz regimen

 

Irinotecan 180 mg/m2 IV/90 min day 1 only

LV 200 mg/m2 IV/2 hrs days 1-2

5FU 400 mg/m2 IVB days 1 then 600 mg/m2 CIV x 22 hrs

Repeat every 2 wks

 

Dose Modifications:

Level -1: Irin 150, LV 200, 5FU bolus 320, 5FU inf 480

Level -2: Irin 120, LV 200, 5FU bolus 240, 5FU inf 360

 

ILF - Saltz
(Saltz Regimen, ASCO 898 5/99)

RR = 49%. Less mucositis & neutropenic fever than 5FU/LV.

Irinotecan      125 mg/m2 IV/90min, then
LV                20 mg/m2 IV, then
5FU              500 mg/m2 IV

Give weekly 4wks out of 6.
Caution: T Bili > 2 or prior pelvic/abd radiation, elderly (>65).
RR = 49%. Less mucositis & neutropenic fever than 5FU/LV.

Dose modifications:

ANC >= 1.5 -- No change
1.0 - 1.49 -- Dec one level
0.5 - 0.99 -- Omit dose, then decrease one level next course
< 0.5 -- Omit dose, then decrease 2 levels

(Similar for plts)

Neutropenic fever: Omit dose, then decrease 2 levels

Diarrhea:

0-3 stools/day -- No change
4-6 -- decrease 1 level
7-9 -- omit dose, then decrease 1 level
>= 10 -- omit dose, then decrease 2 levels

Mucositis/stomatitis: decrease only 5FU.

Level -1:
Irinotecan 100 mg/m2
LV 20 mg/m2
5FU 400 mg/m2

Level -2:
Irinotecan 75 mg/m2
LV 20 mg/m2
5FU 300 mg/m2

In renal failure patients on dialysis, use the Saltz regimen at Level -1 or -2, but give 3 weeks on, 1 week off. Do NOT use infusion 5FU as there are no data on how this works. Same for capecitabine.

 

MITOMYCIN
(Conti, CANCER 75:769, 1995)

Mito-C 10 mg/m2 IVB q 6wks. 4/24 PR (17%)

 

IRINOTECAN (Camptosar[R]) Old name: CPT-11

Premed: Kytril 1mg + Dex 10mg + atropine 0.5mg

125-150 mg/m2 IV/90 min weekly x 4.
Repeat q 6 wks (ie 4 on/2 off) OR 150-250 mg/m2 IV/90 min q 2wks.

(May be better tolerated resulting in greater dose intensity)

Results in 15-20% RR compared with <5% for other regimens used 2nd line in past.

 

INFUSIONAL 5-FU (Lokich: JCO 7:425, 93)

Dose: 300 mg/m2/d CIV by infusion pump

If toxicity occurs (hematologic, mucositis, diarrhea, hand-foot syndrome) interrupt until resolution then decrease by 50 mg/m2/d.

5FU 300 mg/m2/d CIV d1-28 q 5wks

(This regimen was shown to have less toxicity than other regimens in recent SWOG trial with trend towards longer survival. It showed no benefit to modulation with LV. [JCO 6/95] Bottom line: balance bolus 5FU convenience with lower toxicity of infusional 5FU.)

Weekly 5FU/LV

LV    20 mg/m2 IV then
5FU 425 mg/m2 IVB

5FU/LV (Low Dose) (Preferred by Moertel NEJM 330:1136, 4/94)

LV    20 mg/m2 IV then 5FU 425 mg/m2 IVB
Give daily x 5 days

Repeat at 4 wks, 8wks, then q 5wks
Tox: counts, mucositis

5FU/LV (High Dose) (JCO 12:14 1/94)

LV 500 mg/m2 IV/2 hrs then
5FU 600 mg/m2 IVB 1hr after LV started
Give weekly x 6, then off 2 wks (8 wk cycle)

Tox: diarrhea, more likely to require hospitalization than above regimen

FOLFOX-6 (Eur J Cancer 35:1338, 9/99 Maindrault-Goebel, deGramont)

Oxaliplatin 100 mg/m2 IV/2 hrs (at same time as LV) day 1 only

Leucovorin 400 mg/m2 IV/2 hrs day 1, then

 

5FU 400 mg/m2 IVB followed by

5FU 2400-3000 mg/m2 CIV over 46 hrs

Repeat every 2 weeks.

This led to 27% PR, 45% had stable disease. Only 36% received 90% or more of the oxaliplatin due to toxicity. 46% overall experienced grade 3-4 toxicity.

FOLFOX-4 (JCO 18:2938, 8/2000)

Oxaliplatin 85 mg/m2 IV/2 hrs (at same time as LV) day 1 only

LV 200 mg/m2 IV/2 hrs then

5FU 400 mg/m2 IVB then

5FU 600 mg/m2 CIV/22 hrs

Repeat LV, 5FU bolus, and 5FU infusion day 2 (which starts at end of day 1 infusion)

Repeat every 2 weeks.

COLON: Cetuximab

 

ENDOMETRIAL

Hormonal

Medroxyprogesterone 400-800mg IM weekly
OR
Megestrol acetate 40-80 mg PO qid OR
TAM     20 mg QD RRs to parenteral progestins of about 10% are reported in patients w advanced or recurrent disease. Duration usually < 1yr.

Prelim data suggest that patients w well-differentiated lesions should be selected for progestin therapy. ER+/PR+ tumors seem to respond better than those neg for both receptors. Well-diff tumors more often pos than poorly diff tumors.

TAM has activity, but low, ~10%

Single Agent Chemo

DOX 50-60 mg/m2 q 3wk
(RR = 20-40% MS = 7mon)

CDDP  50-100 mg/m2
(RR = 4-41%)

CBDCA 400 mg/m2 q 4wk
(RR = 30%)

Combination Regimens

CTX    400 mg/m2 d1 
DOX    40 mg/m2 d1
Repeat q 4wk
(RR = 17-27% MS = 6mon)


CDDP 60 mg/m2 d1
DOX    50-60 mg/m2 d1
Repeat q 3-4wk
(RR = 33-81%)

Esophagus – Metastatic (JCO 17:3270 10/99)

 

CDDP 30 mg/m2 (give first)

Prehydrate with 500 cc NS/30-60 min

Irinotecan 65 mg/m2 IV/30 min (give after CDDP)

Add atropine if diarrhea or cramping within 1 hour of irinotecan.

Give weekly x 4, repeat q 6 weeks

 

RR 57% CR 6%
Med Duration 4 months MS 15 months

Esophagus – CDDP/5FU/RT

If want to give RT, use 5FU 225-300 mg/m2/d CIV M-F instead of irinotecan.

CDDP 75 mg/m2 d1

5-FU 1000 mg/m2/d CIV d1-4

Repeat wks 1, 5, 8, 11

 

XRT 200 cGy/d to 3000cGy, then boost to 5000

(NEJM 326:1593, 1992)

CDDP 100 mg/m2        d1      
5-FU    1000 mg/m2/d CIV d1-5
Repeat q 4wk

CDDP 75 mg/m2          d1      
5-FU    800 mg/m2/d CIV d1-5
XRT
Repeat q 3wk

CDDP  20 mg/m2          d1-5   
5-FU                900 mg/m2/d CIV d1-5
Etop                 90 mg/m2          d1,3,5
Repeat q 4wk

CDDP              20 mg/m2          d1-5   
MTX                200 mg/m2        d1,15
LV       15 mg IM x 4 doses 24h p MTX
Repeat q 4wk

RRs = 42-64% w survival 16-40wk

Chemo combined w RT improves survival for localized disease better than RT alone.

 

ESOPHAGUS

Neoadjuvant, Metastatic

Weekly RT + Platinum/Taxane

Can use combination of these drugs in these doses:

Cisplatin 25-30 mg/m2
Carboplatin AUC 2

Taxol 45 mg/m2
Taxotere 30-35 mg/m2

Neoadjuvant (Cancer J Sci Am 5:89, 1999)

 

Taxol 200 mg/m2 IV/1 hr days 1,22

Carbo [AUC 6] days 1,22

5FU 225 mg/m2/d CIV days 1-42

 

RT: 4500cGy in 180cGy fractions days 1-42

 

After the above, re-evaluate and resect within 6 wks.

46% CR and another 30% with only minimal residual disease

Some think there is no benefit to adding Taxol and recommend only 5FU/CDDP.

FLP
(Hoff, Ann Thor Surg 56:282, 93)

Week 1 & 4:

CDDP  100 mg/m2 d1
5FU     800 mg/m2 d1-4
LV 50 mg/m2 q6h x 4d

XRT     1000 cGy/wk wks 1-3

Assess/operate wk 8

21% PR           MS 24 mon
No additional benefit CR vs PR

ESOPHAGUS: Photofrin

(porfimer Na)

For palliative therapy of constriction due to cancer. It is given IV, then activated by non-thermal laser passed into esophagus. Activation --> production of free-radicals that kill cancer cells.

 

GASTRIC (Neoadjuvant, Adjuvant, Metastatic)

NEOADJUVANT
RTOG 99-04

5FU 200 mg/m2/day CIV days 1-21
LV 20 mg/m2 IV bolus days 1,8,15,22
CDDP 20 mg/m2 IV days 1-5
Repeat on a 28 day cycle for two total cycles, then

5FU 300 mg/m2/day CIV Mon-Fri during radiation therapy
Taxol 45 mg/m2 IV/3 hours weekly x 5 weeks, then

Surgery

 

ADJUVANT
New Engl J Med 345:725, Sep 2001

5FU 425 mg/m2 + LV 20 mg/m2 QD x 5 days (similar to Mayo regimen), then

 

RT 4500 cGy/5 weeks. Give 5FU 400 mg/m2 + LV 20 mq/m2 days 1-4 and on last 3 days of RT.

 

One month after RT, give 2 more cycles of 5FU/LV (425/20) QD x 5.

Results: 64% of patients completed therapy. 73% had grade 3-4 toxicity. 1% death from toxicity. 44% improvement in RFS, and 28% improvement in OS with median survival 42 months (vs. 27 months in the no treatment arm).

 

FAMTX

For unresectable Gastric Ca

MTX       1500mg/m2 IV d1
5FU        1500mg/m2 IV d1
LV          15mg/m2 po q6h x 48 hrs
DOX       30mg/m2 IV d15

Repeat q 4wks

RR-33%

Notes:

1. Prehydrate and alkalinize to get urine pH > 7.0 before giving MTX. Check urines to keep pH >7.
2. 5FU is given 1 hr after MTX.
3. Leucovorin begins 24 hrs after MTX. Check levels at 12 and 24 hrs.
4. As long as MTX levels < 10-6 to 10-8 range, then can keep on low dose rescue (15 mg/m2). If levels higher, then
increase LV to 50-100 mg/m2 and continue until plasma MTX level is < 50nM. (See Methotrexate Levels)
5. LV comes in 5 and 25mg tabs.

 

 FAM

5FU              600 mg/m2 d1,8,20,36
DOX             30 mg/m2 d1,29
MitoC           10 mg/m2 d1
Repeat q 8wk

Monitor: cum BM, cum heart, HUS
RR = 30%. MS = 22-29wk
AIM 93:533, 1980

FAP

5FU                 300 mg/m2 d1,8,15,22
DOX                30 mg/m2 d1
CDDP  100 mg/m2 d1
Repeat q 4wk

RR= 30%. MS = 32wk

EAP

Etop                 120 mg/m2 d4-6
DOX                20 mg/m2 d1,7
CDDP  40 mg/m2 d2,8
Repeat q 3-4wk

RR = 30%. MS = 24-72wk
Preusser, JCO 7:1310, 1989

ELF

Etop                 120 mg/m2 d1-3
LV                   300 mg/m2 d1-3
5-FU                500 mg/m2 d1-3
Repeat q 3-4wk

RR = 52%. MS = 44wk

EFP (neoadjuvant)

Etop                 80 mg/m2         d1,3,5
5-FU                900 mg/m2 CIV d1-5
CDDP              20 mg/m2         d1-5
Repeat q 4wk

RR = 88% MS = 16-56wk
Ajani, 6th Int Conf on Adj Therapy of Ca, Proceedings, 1990

FAME

5FU                 350 mg/m2 IV d1-5, 36-40
DOX                40 mg/m2 IV d1 36
Methyl-CCNU 150 mg/m2 PO d1

Repeat q 10wk

PFL

CDDP  25 mg/m2/d CIV d1-5
5FU     800 mg/m2/d CIV d2-5
LV       500 mg/m2/d CIV d1-5
Repeat q 4wk

LV rescue 25 mg po q6h x 8 doses beginning 24h after MTX

Gastric ca usually responsive to chemo.

 

HEAD/NECK CHEMOTHERAPY

Weekly RT + Platinum/Taxane

Can use combination of these drugs in these doses:

Cisplatin 25-30 mg/m2
Carboplatin AUC 2

Taxol 45 mg/m2
Taxotere 30-35 mg/m2

Wayne State

CDDP 100 mg/m2 d1
5FU     1000 mg/m2/d CIV d1-5
Repeat q 3wk

RR = 25-70% w survival 4-9 mon

5FU/CDDP/XRT

CDDP  70 mg/m2 d1
5FU     800 mg/m2 QD x 5 days
XRT     200 cGy/tx x 5 days
Repeat q 3wks x 3-5 cycles

 PALLIATION: Taxol and Carboplatin

 

HODGKIN'S DISEASE

ABVD

Dox      25 mg/m2 IV d1,15     
Bleo     10 u/m2 IV d1,15        
VBL     6 mg/m2 IV d1,15
DTIC   375 mg/m2 IV d1,15

Repeat q 4wks

Test dose for Bleo

MOPP

Mustard           6 mg/m2 IV d1,8         
VCR    1.4 mg/m2 IV d1,8
Procarbazine 100 mg/m2 po d1-14 (50mg caps)
Prednisone 40 mg/m2 po d1-14

Repeat q 4wk

CVPP/ABO
Used at British Columbia Cancer Agency for patients who cannot take ABVD due to specific drug contraindication. Omit whichever drug the patient cannot take. This allows delivery of several other active drugs. (from Dr. Joseph Connors)

Day 1:
Cytoxan     600 mg/m2 IV
Vinblastine     6 mg/m2 IV
Procarbazine 100 mg/m2 po days 1-7
Prednisone 45 mg/m2 po days 1-14

Day 8:
Doxorubicin  35 mg/m2 IV
Hydrocortisone 100 mg pre-Bleomycin
Bleomycin 10 u/m2
Vincristine 1.4 mg/m2 (no cap)

Dose adjustments:         Day 1: If ANC < 0.8, give full dose, but add G-CSF 300 mcg days 9-13 (5 days).
                                    Day 8: If ANC < 0.8, omit doxorubicin.
Use growth factors only after need demonstrated, and use as needed to keep patient on schedule.

Cycle every 28 days for minimum of 6 cycles and maximum of 8.

MOPP/ABVD (Hybrid)

Mustard                       6 mg/m2 IV d1
VCR                1.4 mg/m2 IV d1
Procarbazine 100 mg/m2 PO d1-7 (50mg caps)
Prednisone 40 mg/m2 PO d1-14
DOX                35 mg/m2 IV d8
Bleo                 10 u/m2 IV d8
VBL                 6 mg/m2 IV d8
Repeat q 4wk

(Test dose for Bleo)

ChlVPP

Chlorambucil 6 mg/m2 PO d1-14        
VBL     6 mg/m2 IV d1,8
Procarbazine 100 mg/m2 PO d1-14 (50mg caps)
Prednisone 40 mg/m2 PO d1-14
Repeat q 4wk

Current regimens --> CR 80-95% in Stage III-IV disease.
30% relapse requiring salvage therapy.
Appropriate therapy will cure an additional 10-15% of patients.
Overall, 75% of patients w advanced H are curable.

Those w CR>1yr respond to therapy. Those who relapse at <1 yr do NOT usually have durable 2nd remissions with standard treatments.
Maintenance therapy does NOT improve RR or survival.

 

 

LUNG: NSCLC CHEMOTHERAPY (Adjuvant, Metastatic)

Adjuvant

Carboplatin AUC 5 and Taxol 200 mg/m2 q 3 weeks x 4 OR

CDDP 50 mg/m2 days 1, 8
Navelbine 25 mg/m2 weekly x 4
Give q 4 weeks x 4 cycles

Metastatic

CARBO/TAXOL

Taxol 200 mg/m2 IV/1hr
Carbo  AUC=6
Give q 3wks

 

MS 10 months, 1YS 42%, Overall RR 28% (JCO 20:3578 7/02)

TAXOL/GEMCITABINE

Taxol 200 mg/m2 IV day 1

Gemcitabine 1000 mg/m2 days 1, 8

Give q 3 weeks

 

Equivalent to Taxol/carboplatin with MS 10 months and 1 YS 41%. Overall RR 35%. (JCO 20:3578 7/02)

PEMETREXED (ALIMTA)

As 2nd line therapy ORR was same as Taxotere (9%) with similar MS (8 months) in NSCLC, but was less toxic.

 

500 mg/m2 IV over 10 minutes Q3 weeks

 

Premed:

Folate 1 mg daily beginning 1-2 weeks prior to starting chemotherapy until 3 weeks after last dose of pemetrexed.

Vitamin B12  1,000 mcg IM 1-2 weeks before pemetrexed and Q 9 weeks (every third cycle) until after discontinuation.

Decadron 4 mg BID on day before, day of, and day after pemetrexed to prevent skin rash.

 

Mechanism: Antifolate drug with multiple targets. Inhibits TS, DHFR and glycinamide ribonucleotide formyl transferase.

Toxicities: Hematologic, rise in ALT

WEEKLY CARBO/TAXOL/XRT

For Stage IIIa/b
[ASCO Proc #1608, 1997]

Taxol 45 mg/m2 IV/3h
Carbo 100 mg/m2 IV
XRT 1.8 Gy/fx x 6-7wks to 60-65Gy

 CARBO/GEMCITABINE
(Sem Onc 55:51 8/98)

Gem  1000 mg/m2 IV/30min d 1,8
Carbo [AUC 5.2] d 1
Repeat q 3-4 wks

(RR = 30-60%)

WEEKLY TAXOTERE

35 mg/m2 IV/1 hr weekly x 6
(8 wk cycle)
Premed: Dex 4 mg IV

CARBO/VP16

CBDCA        300 mg/m2 IV d1
VP16 100 mg/m2 IV d1-3
Repeat q 3-4wks

Alternate: Can dose Carbo using AUC=5-7

NVB    30 mg/m2 IV weekly.

Adjust: ANC 1000-1499: 15 mg/m2
          ANC < 1000 : Hold

Cisplatin/VP16

CDDP           60-120 mg/m2             d1
VP16            80-120 mg/m2             d1-3
Repeat q 3wk

ICE

IFOS 5 gm/m2 IV, d1 24 hr infusion with Mesna
Carbo 300 mg/m2 iv, d1 1hr infusion
ETOP 120 mg/m2 iv, d1&2, 240 mg/m2 po, d3

RRs ~ 30%, but short duration

 

LUNG: NSCLC STAGE III ADJUVANT
(ChemoRT)

Taxol 50 mg/m2 + Carbo AUC=2
Give weekly thru RT (6600cGy), then

Taxol 200 mg/m2 + Carbo AUC=6

Give q3wks x 2 cycles

 

LUNG: SMALL CELL CHEMOTHERAPY

Extensive Disease, Limited Stage, Recurrent

Limited Stage

Carbo/VP16

Carbo AUC=6 day 1 only
Etoposide 100 mg/m2 days 1,2,3

Give q 3 weeks x 6

CARBO/TAXOL/ETOPOSIDE

Taxol 200 mg/m2
Carbo AUC = 6
Oral etoposide 50/100 mg alternating days 1-10.

- Can also be given with RT in patients with Limited Stage.

(Hainsworth, Greco: Oncology 12:31, 1/98.

In other studies the addition of Taxol to carbo/vp16 did NOT make a difference in Limited stage disease, but it make a small difference in Extensive stage dz.

Extensive Disease

CDDP/CPT-11
For Extensive Disease (Proc ASCO 2000 #1887 Updated at ASCO. Later published in NEJM 346:85 1/10/02)

CDDP 60 mg/m2 d 1
CPT-11 60 mg/m2 d 1,8,15

Repeat q 4wks x 4 courses

Dose Adjustments:

·        Skip irinotecan on day 8 or 15 if:
WBC < 2
Plt < 50
Diarrhea.

 

·        Resume when:
WBC 3.5
Plt > 100 and
Diarrhea resolved.
Reduce subsequent irinotecan by 10 mg/m2.

Comparison to cisplatin/etoposide:
RR             85% v 68%
CR               3% v   9%
MS 13 months v 9.5 (p .0021)
1 YS 58% v 38%
2 YS 20% v 5%

 

 

TAXOL/CARBO (JCO 19:1320 3/01)

Taxol 200 mg/m2 over 1 hr
Carbo AUC=6
Q 3 wks x 6

In patients with extensive stage disease:
RR 65%
CR 11%
NR 24%
DFS 5.5 months
MS 9 months

Recurrent Disease

TOPOTECAN (HYCAMTIN) - For Recurrent Disease

1.5 mg/m2/d IV/30min x 5 d
Repeat q 3wk

15-20% RR in previously txd patients.

CDDP           80 mg/m2 d1
VP16 100-120 mg/m2 d1-3
Repeat q 3wk

CR 13%
RR 67%
MS 10 mon
1 YS 40%

MANTLE CELL / CASTLEMANS

Hyper CVAD (MDACC)

For aggressive hyaline vascular Castlemans that does not respond to surgery.

REQUIRES DOUBLE LUMEN CENTRAL LINE:

- CTX 300 mg/m2/dose in 500 ml D5W IV/3 hrs q 12h x 6 doses
- Mesna 600 mg/m2/dose in 2000 ml D5NS CIV/24 hrs QD x 3 days. (Begin 1 hr prior to CTX and complete by 12 hrs after last dose of CTX.)
- 12 hours after last dose of CTX, give:
            - DOX 25 mg/m2/d CIV QD x 2 days (Days 4-5). (If Bili > 2, adjust DOX.)
            - VCR 2 mg IV on Days 4, 11

Rxs:
Decadron 4 mg #80 Sig: 40 mg po QD d 1-4, 11-14
Levaquin 500 mg po QD x 10
Diflucan 100 mg po QD x 10
Valtrex 500 mg po QD x 10
Compazine 10 mg po q4h prn
G-CSF 5 mcg/kg QD days 6-15 or until ANC > 10K

Repeat q 3 wks.

 

 

MELANOMA: ADJUVANT IFN
(JCO 14:7 1996) ECOG

For patients with >4 mm deep OR LN+ disease.

IFNa2b 20 mu/m2/day 5 days/wk x 4 wks, then
10 mu/m2 SQ TIW x 48 wks

RFS 0.98 yrs --> 1.72
OS 2.8 yrs --> 3.8 yrs
Effect most noted in LN+ patients.

Tox: severe 67%. Life threatening 10%. >80% patients were able to complete the course.

 

MELANOMA: METASTATIC

OUTPATIENT BIOCHEMO
(Cancer J Sci Am 3:Supp 29, '97)

Dacarbazine 660 mg/m2 IV d1
CDDP 75 mg/m2 IV d1
Carmustine (BCNU) 150 mg/m2 IV (EVERY OTHER CYCLE)
IL2 3 mu/m2 SQ days 3-9
IFNa2a 3 mu/m2 SQ day 3, then 5 mu/m2 (but no > 9mu) days 5,7,9
Indocin 25 mg qid d 2-9
Tylenol 650 mg qid d 2-9
Axid 150 mg bid d 2-9
Repeat q 3-4 wks.

 

Patients who get CR or stable PR for at least 4 wks --> maintenance:
IFNa2a 5mu/m2 (no > 9mu) SQ TIW x 1 year.

CR 19%
RR 42%
MS 12 months

 

LEGHA REGIMEN
(JCO 16:1752, 5/98)

CDDP 20 mg/m2 IV d 1-4
DTIC 600 mg/m2 IV d 1-4
Vinblastine 1.6 mg/m2 IV d 1-4
IL2 9 mu/m2/d CIV x 4d
IFNa 5 mu/m2 SQ d 1-5, then qod x 4 more doses.

Repeat q 21-28 days.

Notes:

1. Prehydrate CDDP with 1 L NS/2 hrs
2. Maint IV: D51/2NS + 20 meq KCl + 8 meq MgSO4 at 75 cc/hr.
3. Premeds: Zofran 32 mg + Tylenol. Add Naproxen 375 mg bid if fever, Demerol 50mg IV q 4-6h prn chills.
4. Ck BP q 4h. If sys < 100, increase fluids to 100-125 cc/hr. If BP < 90, bolus with 500 cc NS. If remains low, give dopamine 5 mcg/kg/min to maintain sys BP > 90.
5. Ck Cr prior to d3 CDDP. If > 1.6, hold CDDP and start low dose dopamine (5 mcg/kg/min). If Cr drops back to 1.5 or less, may be able to give final dose of CDDP (day 4).
6. Monitor 24-48 hrs after completion of IL2. D/C if no nausea, fever, pt eating, and Cr < 1.5.

HI-DOSE IL-2
JCO 17:2105, 7/99

IL-2 360,000 IU/kg IV q8h x 14 doses. Repeat in 6-9 days, then q 6-12 wks in stable or responding patients.

Doses withheld (rather than reducing dose) if: hypotension requiring vasopressor support; respiratory distress; arrhythmias; cardiac dysfunction or ischemia; CNS toxicity (confusion, agitation).

16% RR with 6% CR. Long duration responses. Toxicity severe, but reversed quickly.

MESOTHELIOMA

CISPLAT 100 MG/M2 DAY 1
MTX    30 MG/M2 DAYS 8,15,22
VINBLASTINE 3 MG/M2 DAYS 8,15,22

Repeat Q 28 DAYS

Could Consider Carboplatin @ 325 Mg/M2 As Substitute For Cisplatin

Response 53% (9/17)
Proc ASCO 1995, #1380

 

MYELOMA CHEMOTHERAPY

Melphalan/Decadron Melphalan 0.25 mg/kg QD x 4d
Decadron 40 mg QD x 4 (initially may want to do three 4-day courses per month like VAD)

Cytoxan can sub for melphalan. Use 150-250 mg/d x 4d.

Comes in 50 and 25mg tabs.

VAD (University of Arkansas)

VCR 0.5 mg/d CIV d 1-4 (note: not /m2)
DOX 10 mg/m2/d CIV d 1-4
Decadron 40 mg/d po d 1-4, 9-12, 17-20

Prophylactic medications:
Acyclovir 400 mg BID Mon and Thurs
Diflucan 100 mg po QOD
Zantac 150 mg BID
Bactrim DS BID MWF
Coumadin 1 mg QD if on thalidomide

Repeat q4 wk x 4 cycles beyond point of max reduction of M protein. Response is usually rapid (usually 1 cycle), so can usually assess response after 2 cycles.

45-75% RR as salvage therapy.
Very little, if any, cardiotoxicity, and little myelosuppression. Most of the toxicity observed is from Decadron.

DCEP (University of Arkansas)

Decadron 40 mg/day po days 1-4
Cytoxan 400 mg/m2/day CIV days 1-4
Etoposide 40 mg/m2/day CIV days 1-4
Cisplatin 15 mg/m2/day CIV days 1-4

Adjustments for CDDP: Cr <= 1.5 --> full dose. Cr 1.6-2.0 --> 10 mg/m2. Cr 2.1-3.0 --> 7.5 mg/m2. Cr > 3.0 --> 0 mg (hold cisplatin).

The daily dose of cyclophosphamide, etoposide, and cisplatin will be mixed in a 1L bag of NS to be infused over 24 hrs. Also run maintenance: 1L NS + 20 meq KCl + 8 meq MgSO4 CIV/24 hrs (42 cc/hr). The chemotherapy and maintenance cannot be run together due to incompatibility of chemotherapy with KCl and MgSO4.

On Day 6 start G-CSF 5 mcg/kg until ANC > 2000 for 2 consecutive days.

Prophylactic medications:
Acyclovir 400 mg QD
Levaquin 500 mg QD
Diflucan 200 mg po QD
Zantac 150 mg BID
Coumadin 1 mg po QD if on thalidomide
Thalidomide 400 mg QHS
Lovenox 40 mg SQ QD during thrombocytopenia < 50K

 

HD METHYLPREDNISOLONE (Abeloff p 2060)

Give 2gm IV TIW x at least 4wks. If response, then reduce to twice, then once weekly.

Leads to response in 25% of patients refractory to alkylators.

Fewer side effects than HD Decadron.

MELPHALAN/PREDNISONE

Melphalan 8mg/m2 po pre breakfast QD x 4 (2mg tabs)
Prednisone 60mg/m2 po post breakfast QD x 4

Repeat q 4-6 wks for at least 3 courses and no longer than 1yr.

Melphalan 6 mg/m2 QD x 7
Prednisone 100 mg/m2 QD x 7

Repeat q 4 wks x 6 cycles

Because GI absorption of melphalan is unpredictable, mild granulocytopenia (ANC 1000-2000) or plt < 1000 should be confirmed 3 wks after tx to ensure an effective dose was given. If no response, increase dose by 20%.

40% patients will respond with 75% reduction in M protein, a 95% reduction in BJ protein, and <5% plasma cells in BM. Note that response is not a predictor of survival. In fact, big response may actually have worse prognosis.

Overall MS=2-3y, but prognosis highly dependent on extent of disease and response to treatment. Median remission = 2yrs.

VAP

VCR    1.5 mg IV d1
DOX    35 mg/m2 d1
Pred 45 mg/m2 po days 1-5, 9-13, 17-21

Repeat q 25d

Blood 62:572, '83

HD Decadron (AIM 105:8-11, 1986)

DEXAMETHASONE 40 MG PO DAYS 1-4, 9-12, 17-20

Repeat q 4 wks

Same as Decadron in VAD. Induces rapid remission, but 15% lower RR than VAD. Has induced PR in 25% patients who fail primary melph/pred, prolonging survival by 1yr.

VBMCP (Same as M2, but dosed by m2, from Skeel)

VCR 2 mg iv d1          
CTX 400 mg/m2 iv d1
BCNU 20 mg/m2 iv d1
Melphalan        8 mg/m2 po d1-4
Prednisone 40 mg/m2 po d1-7 (all cycles)
Prednisone 20 mg/m2 po d8-14 (cycles 1-3 only)
Repeat q 5 wks x 1yr

72% RR with MS=28-30 mon, 5YS=26%.

M-2 Regimen

VCR 0.03 mg/kg iv d1
CTX    10 mg/kg iv d1
BCNU 0.5 mg/kg iv d1
Melphalan        0.25 mg/kg po d1-4
Prednisone       1 mg/kg po d1-7. Taper over next 2 wks.

Repeat q 5 wks

EDAP

VP16   100 mg/m2/d CIV d1-4
Decadron 40 mg/m2 po d1-5
Ara-C  1000 mg/m2 IV d5
CDDP 25 mg/m2/d CIV d1-4

Only regimen besides VAD with established efficacy in refractory myeloma. In 20 patients, treatment --> RR=40% and MS 4.5mon. May be as effective as VAD.

VMCP

VCR    1 mg iv d1
Melphalan         6 mg/m2 po d1-4
CTX    125 mg/m2 po d1-4
Pred                 60 mg/m2 po d1-4
Repeat q 3-4 wks

VBAP

VCR    1mg iv d1
BCNU 30mg/m2 iv d1
ADRIA            30mg/m2 iv d1
Pred                 60mg/m2 po d1-4
Repeat q 3-4wks

VCAP

VCR    1mg/m2 (max 1.5) iv d1
CTX    125mg/m2 po d1-4
DOX    30mg/m2 iv d1
Pred     60mg/m2 po d1-4

IFN-a

IFN-a  1-3 mu/m2 sq TIW

Prolongs plateau phase by 6-9 months, but no increase in survival. Falling into disfavor.

 

MYELOMA: DTPACE

CDDP 10 mg/m2 CIV x 4d
Etop 40 mg/m2 CIV x 4d
CTX 400 mg/m2 CIV x 4d
Mix the above in 1L NS

DOX 10 mg/m2 CIV x 4d (mix in at least 50 ml D5W to run over 24hrs)
Dex 40 mg po QD x 4d
Thalidomide 400 mg po qHS

Aredia

Zofran 30 mg IV QD x 5d
Torecan 10 mg q6h x 5d

 

NHL CHEMO – Aggressive Disease

CHOP + Rituxan

Give Rituxan 375 mg/m2 d1
CHOP on d3

JCO 19:389 1/01

CHOP

CTX    750 mg/m2 IV D1
DOX    50 mg/m2 IV D1
VCR    2 mg/m2 IV D1
Pred     100 mg PO D1-5
Repeat q 3wks

(Dox can be given CIV/48-96h)

m-BACOD

MTX                200 mg/m2 IV d8,15
Leucovor 10 mg/m2 PO q6h x 6
(Give 24h after MTX)
Bleo                 4 u/m2 IV d1
DOX                45 mg/m2 IV d1
CTX                600 mg/m2 IV d1
VCR                1 mg/m2 IV d1
Dexameth 6 mg/m2 PO d1-15
Repeat q 3wk

ProMACE/CytaBOM (Short Course - 16 wks)

CTX                525 mg/m2 IV d1 (Repeat every other wk)
DOX                22 mg/m2 IV d1 (Repeat every other wk [odd])
Etop                 110 mg/m2 IV d1 (Odd weeks)
Ara-C              300 mg/m2 IV d8 (Repeat even weeks)
Bleo                 5 u/m2 IV d8
VCR                1.4 mg/m2 IV d8
MTX                120 mg/m2 IV d8
Leucov 25 mg/m2 PO q6h x 6
(Give 24 h after MTX)
Pred                 60 mg/m2 PO d1-14
Repeat: 14d on, 7 off
Prophlactic Bactrim DS BID during treatment

ProMACE/CytaBOM (Standard)

CTX                650 mg/m2 IV d1
DOX                25 mg/m2 IV d1
Etop                 120 mg/m2 IV d1
Ara-C              300 mg/m2 IV d8
Bleo                 5 u/m2 IV d8
VCR                1.4 mg/m2 IV d8
MTX                120 mg/m2 IV d8
Leucov 25 mg/m2 PO q6h x 6 24 h after MTX
Pred                 60 mg/m2 PO d1-14
Repeat q 3wk

Prophlactic Bactrim DS BID uring treatment

COP-BLAM III

CTX    350 mg/m2 IV  d1,22
VCR    1 mg/m2/d CIV            d1-2
             1 mg/m2 IVP   d22
Procarba 100 mg/m2 PO          d1-5,22-26
Bleo     7.5 u/m2/d IVP            d1
            7.5 u/m2/d CIV            d1-5
Pred     40 mg/m2 PO   d1-5,22-26
DOX    35 mg/m2 IV    d1,22
Repeat q 6wk

MACOP-B

MTX    100 mg/m2 bolus, then
            300 mg/m2 IV/4h         wk2,6,10
Leucov 15 mg/m2 PO q6h x 6 24h p MTX
DOX    50 mg/m2 IV wk1,3,5,7,9,11
CTX    350 mg/m2 IV wk1,3,5,7,9,11
VCR    1.4 mg/m2 IV wk2,4,8,10,12
Bleo     10 u/m2 IV wk 4,8, 12
Pred     75 mg PO QD x 12 wks (then taper over 2 wks)

Prophylactic Bactrim

ESHAP

Etoposide         40 mg/m2 IV d1-4
CDDP              25 mg/m2d CIV d1-4
Ara-C 2 gm/m2 IV d5 only (immediately upon completion of VP16/CDDP)
Methylprednisolone 500 mg/d IV d1-4

Repeat q 4wks

--------------------------------------

In advanced low-grade NHL, no superior approach. Aggressive therapy --> inc CR, but no diff in survival.
Cure in high-grade NHL depends on achieving a CR with initial treatment.
In setting of CR in high grade, no benefit to maintenance treatment.
In high grade, no regimen clearly superior to CHOP. However, CHOP clearly inadequate for patients w poor prognostic features.
For high grade, dose attenuation compromises efficacy. Failure to administer a regimen at max doses significantly compromises patient’s chance for a CR.

 

NHL SALVAGE (ie, CHOP FAILURES) EPOCH, ESHAP, MINE-ESHAP, DHAP, DICE, DHAX, ICE

EPOCH (JCO 8/93)
For low, intermediate, or high-grade NHL relapsed or failed previous treatment. Cheson at NCI thinks better than ESHAP.

Etoposide 50 mg/m2/d CIV x 4d (give thru separate line)
VCR 0.4 mg/m2/d CIV x 4d
DOX 10 mg/m2/d CIV x 4d
(Give VCR and DOX through same line)
CTX 750 mg/m2 IV on d 6
Prednisone 60 mg/m2 po d 1-6

Repeat q 3 wks

Modifications for counts:

ANC > 1500            No change
1000-1500                Reduce CTX by 25%
<1000                       Hold chemo

If ANC nadir < 500 Reduce CTX an additional 25%

Pneumocystis prophylaxis w Bactrim DS BID x 3d/wk OR aerosolized pentamidine. Continue thru all cycles.

ESHAP

Etoposide 60 mg/m2 IV d1-4
CDDP  25 mg/m2/d CIV d1-4
Ara-C 2 gm/m2 IV bolus d5 only (immediately upon completion of VP16/CDDP)
Methylprednisolone 500 mg/d IV d1-4


Repeat q 4wks

Adjustments:

If >65 or pelvic RT:

Etoposide 47.5 mg/m2/d
Ara-C 1 gm/m2

 

CDDP acc to Creat:

1.5-2.0 -- decrease 33%
2.1-2.5 -- decrease 50%
>2.5 Delete from regimen

RR 69% (48% CR, 21% PR)
MS 2yrs
TTF 12 mon.

MINE-ESHAP
(JCO 13:1734 7/95) MDACC

All histologies. Patients who were not known to be refractory to any of the drugs (ie, had not relapsed within 6 months of prior treatment. Patients treated first with MINE and restaged q 2 months.

- If CR, then treated with 6 cycles MINE followed by 3 of ESHAP.
- If PR, then MINE given to max response, then ESHAP (x 6 if CR, or until max response or no response)

MINE

Mesna 1.33 gm/m2 IV/1hr QD x 3, and 500mg in juice po 4hrs after the Ifos
Ifosfamide 1.33 gm/m2 IV/1hr QD x 3
Mitoxantrone 8 mg/m2 IV day 1
Etoposide 65 mg/m2/d days 1-3

ESHAP (as above)

 

NHL: HIGH-GRADE -- SMALL NONCLEAVED CELL
(Burkitts & non-Burkitts)
(McMaster & Greco, JCO 9:941 6/91)

Regimen consists of 2 cycles. 85% CR rate (no PRs) with 76% durable remission in patients able to complete therapy.

Cycle 1

Before starting: allopurinol, hydration. Consider alk urine.
CTX    1500 mg/m2/d CIV d 1,2
VP16   400 mg/m2/d CIV d 1,2,3
VCR    2 mg/m2 IV d 8,22
Bleo     10 u/m2/d IV d 8,22 (remember test dose)
MTX    200 mg/m2 IV d 15
LV       15 mg/m2 po q6h x 6 start 24h after MTX
Pred     60 mg/m2/d po d 1-7
Start G-CSF day 8 x 10d

Cycle 2
Begins on day 29 if ANC > 1000

Same as above, except:

CTX given on day 1 only
VP16 reduced to 100 mg/m2/d
Add DOX on days 1,2
CTX    1500 mg/m2/d CIV d 1
VP16   100 mg/m2/d CIV d 1,2,3
DOX    45 mg/m2/d IV d 1,2
VCR    2 mg/m2 IV d 8,22
Bleo     10 u/m2/d IV d 8,22
MTX    200 mg/m2 IV d 15
LV       15 mg/m2 po q6h x 6 start 24h after MTX
Pred     60 mg/m2/d po d 1-7

If patients have meningeal involvement, give:
MTX 12mg BIW x 5 doses and whole brain RT (2000 cGy/10 days) concurrently with chemo.

Has been used in HIV+ patients too.

 

NHL: LOW-GRADE - CHEMO

CTX/FLUDARA/RITUXAN

Rituxan day 1 @ 375 mg/m2 first cycle, then 500 mg/m2 subsequent cycles

 

Fludarabine 25 mg/m2 days 2-4
Cytoxan 250 mg/m2 IV days 2-4
Repeat q 3 weeks
Give prophylactic Bactrim DS 1 q MWF

FND/Rituxan

For Stage IV indolent lymphoma or CLL

 

Fludarabine 25 mg/m2 IV days 1-3
Mitoxantrone 10 mg/m2 IV day 1 only
Decadron 20 mg/m2 IV or po days 1-5
Rituxan 375 mg/m2 days 1,8 for the first course. For subsequent courses, give the Rituxan on day 1 only, and shift Fludarabine to days 2-4 and Mitoxantrone to day 2.


Give PCP prophylaxis: Bactrim DS BID on Sat-Sun

FND/CHOP
For bulky low grade

FND

Fludara 25mg/m2 IV d 1,2,3
Mitoxantrone 10mg/m2 IV d 1
Decadron 20mg IV d 1,2,3
Decadron 20mg PO d 4,5
Bactrim DS BID q Sat/Sun

CHOP - give 4 wks after FND cycle

CTX 750 mg/m2 IV d1
DOX 50 mg/m2 IV d1
VCR 2 mg IV d1
Pred  100 mg po d1-5

Bactrim DS BID q Sat/Sun
Continue for 2 cycles after CR (min 6, max 10)
 

OVARIAN

Epithelial

Taxol 175 mg/m2 over 3hrs q 3 wks
Carbo AUC 7.5

Carcinosarcoma
(GOG)

CDDP 20mg/m2 gd x 4
Ifos 1.5 gm/m2 QD x 4

 

RECTAL CA - ADJUVANT TREATMEMT

TNM Stage II/III (Dukes B2/C) - Mayo NEJM 331:502, 8/94
(Listed by weeks rather than days)

Wk 1 5FU 500 mg/m2 IVB x 5d
Wk 5 5FU 500 mg/m2 IVB x 5d
Wk 9-14 5FU 225 mg/m2 CIV during RT. Give until RT finished or tox. XRT 4500 cGy/5 wks w 540cGy boost (total 6wks)
Wk 15-18: 4 week break
Wk 19 5FU 450 mg/m2 IVB x 5d     (NOTE LOWER DOSE 5FU!!)
Wk 24 5FU 450 mg/m2 IVB x 5d     Total: 6 months therapy

TNM Stage II/III (Dukes B2/C) - Mayo NEJM 331:502, 8/94
(As it appeared in the article)

Day 1- 5: 5FU 500 mg/m2 IVB
Day 36-40: 5FU 500 mg/m2 IVB
Day 64: XRT 4500 cGy/5 wks w 540cGy boost (total 6wks)
5FU 225 mg/m2 CVI until RT finished or tox
Day 134-138 5FU 450 mg/m2 IVB
Day 169-173 5FU 450 mg/m2 IVB

 

B2/C RECTAL - (GITSG Man Clin Onc 3rd ed)

Day 1: 5FU 500 mg/m2 IVB x 5d
Day 28: 5FU 500 mg/m2 IVB x 5d
Day 56: XRT 5040cGy (180/d for 6wks)
5FU 500 mg/m2 IVB x 3d
5FU 500 mg/m2 IVB x 3d also given first 3d of last wk of RT
1 mon p RT: 5FU 400 mg/m2 IVB x 5d
2 mon p RT: 5FU 500 mg/m2 IVB x 5d
Alternate: same as above except during RT give 5FU as CIV at dose 225 mg/m2/d

 

DUKES B2/C (GITSG Skeel)

XRT 4320 cGy/5 wks
5FU 500mg/m2 IVB first & last three days of RT and
5FU 350mg/m2 d1-5 beginning wk 11. Repeat q4 wks, escalating dose as tolerated to max 500 mg/m2 up to total of 6 courses.
Subsequently - FU 375mg/m2 d1-5 q
5 wks + mCCNU 130mg/m2 d1 q 10wk

DATA
- Because of anatomy, surgeons can’t achieve wide, tumor-free margins.
- Almost 50% of recurrences are in the pelvis.

RECTAL NEOADJUVANT

5FU/HDLV x 2 months then
5FU 225 mg/m2/d CIV M-F during RT, then
Surgery, then
5FU/HDLV x 2-4 cycles post-op

Alternately, can use Xeloda 825 mg/m2 BID during RT, either given 14 days on/7 off, M-F during RT, or straight through.

One NSABP trial (R-03) gave systemic therapy 1 month -> chemoRT -> 4 months of systemic therapy. Trial closed early due to poor accrual, but showed a trend towards benefit with pre-op therapy.

 

RENAL CELL: BIOLOGIC THERAPY

INTERMEDIATE-DOSE IL2
(Cancer J Sci Am 3:Supp 79, 1997
JCO 21(16):3127, Aug 2003)

72,000 u/kg IV/15 min q8h x 15 doses. (Mix in 50 ml D5W)

Repeat in 7-10 days after finishing first. This constitutes one course.

Creatinine should be < 1.6 before starting. If creatinine rises to more than 4.0-4.5 during treatment, hold until creatinine drops by at least 1.5. Also hold for: arrhythmias, BP < 90, need for pressors, confusion/agitation, O2 sat < 90%, bullous dermatitis. May restart when the problems resolve.

A course may be repeated every 2 months as long as responding or stable disease. Stop if progression or no change after 2 courses.

Premed:
Tylenol 1000 mg po
Benadryl 50 mg po
Compazine 10mg po/IV
Demerol 50mg IV or 150mg po (if pt has rigors)

HD regimen given same way, but at 10x the dose (720,000 u/kg) There have been no differences in survival between HD, LD, and SQ IL2. RRs all around 10-15%. The HD regimen is associated with a higher RR (21%), but also greater toxicity. There was no difference in response between the SQ and LD regimens. The HD regimen may be preferred in patients who can tolerate it. A few patients who achieved a CR may actually be cured. See below.

SUBCUTANEOUS IL2

250,000 u/kg days 1-5, then 125,000 u/kg 5/7d, wks 2-5

SQ IFNa + IL2
(Atzpodien-Germany JCO 13:497, 2/95)

Weeks 1 and 4:

IFNa 6 mu/m2 SQ d 1
IL2 20 mu/m2 SQ d 3,4,5

Weeks 2,3,5,6:

IFNa 6 mu/m2 SQ TIW
IL2 5 mu/m2 SQ TIW

Repeat q 8 wks

CR 6% w med dur 16 mon
RR 25% w med dur 9 mon
Stable disease 36%
Most sxs Grade 1-2

HIGH DOSE IL2
(Yang-NCI SA Cancer J S79)

IL2 720,000 u/kg IV q8h x 14 doses. Wait 7-10 days, then repeat.

Repeat every 2 months until stable disease for 2 months or progression.

CR 8%
RR 19%
Responses tended to be more durable than low-dose IL2 alone.

IFNa + Infusion IL2
(Negrier-France NEJM 338:1272 4/98)

INDUCTION:

IFNa-2a 6 mu TIW
IL2 18 mu/m2/d CIV x 5 days
One wk rest, then repeat once.

MAINTENANCE:

Same as above, but 3 wk breaks between cycles. Total of 4 maint. cycles (6 cycles overall).

RR 18.6%
1 yr event free surv = 20%

 

SARCOMA: MDACC Regimen

(Adria-Ifos-Mesna-VCR)

1. Mesna 1500mg/m2/d = ___ mg in 2L D5W + 100 meq Na acetate + 20 meq K acetate + 4 meq MgSO4 continuous IV/24 hours days 1-4.
2. Antiemetics: Anzemet 100mg + Decadron 10 mg prior to Ifos each day. May repeat at end of last Mesna infusion (day 4).
3. Ifosfamide 2500 mg/m2 = ___ mg + Mesna 500 mg/m2 in 500 ml NS IV/2 hrs day 1.
Ifosfamide 2500 mg/m2 = ___ mg in 500 ml NS IV/2 hrs days 2,3,4.
4. If pt has gross hematuria, give Mesna 500 mg/m2 = ___ mg in 500 ml NS IV/ 1 hr.
5. Vincristine 2 mg IV day 1 only.
6. Adriamycin 25 mg/m2/d = ___ mg/d CIV/24 hrs days 1,2,3.
7. G-CSF 300 mcg SQ days 5-14.
8. Compazine 10 mg po/iv q4h prn nausea.

 

TESTICULAR CA

BEP (Orders)

BLEO  30 u IV d2,9,16
VP16   100 mg/m2/d IV d1-5 (decrease by 20% if prior XRT)
CDDP  20 mg/m2/d IV d1-5
Repeat q 3wk

Only need 1L hydration/d for CDDP

Monitor pulm tox

Williams, NEJM 316:1435, 1987

May also give over 3 days. If so, give Bleomycin 30 mg weekly x 3, Etoposide 165 mg/m2/d days 1,2,3 and CDDP 50 mg/m2/d days 1,2. This gives the same total doses with equal efficacy. Slightly higher incidence of nausea. (JCO 19:1629, 3/01)

PVB

CDDP  20 mg/m2/d d1-5
VLB     6 mg/m2/d d1,2
BLEO  30 u weekly
Repeat q 3wk x 4

Williams, NEJM 316:1435, 1987

VIP      (Dana-Farber) AIM 109:540 1988

VP16   75 mg/m2/d IV d1-5
IFOS   1.2 GM/m2/d CIV d1-5
CDDP  20 mg/m2/d IV d1-5
Mesna  400 mg IV load, then 1.2 gm/m2/d CIV d1-5

Repeat q 3wk x 4

Note: Can also give IFF/Mesna as boluses

 

VIP #2 (Salvage regimen-uses Velban instead of VP16)

VLB     0.11 MG/KG/d d1-2
Ifos      1.2 GM/m2/d CIV d1-5
CDDP  20 mg/m2/d d1-5
Mesna  400 mg/m2 IV 15min pre ifos, then
Mesna  1.2 GM/m2/d CIV d1-5
Repeat q 3wks

AIM 109:540 1988

 

TESTICULAR: BEP ORDERS

BEP:

CDDP days 1-5 as follows:
Prehydrate NS 250 cc IV/1hr
CDDP 20mg/m2 + 12.5gm mannitol in 500cc NS IV/30 min
Posthydrate NS 250cc IV/1hr

Etoposide 100mg/m2 IV/30 min days 1-5

Bleomycin 30 units IV days 2,9,16
(First dose: Give 2 unit test dose. If no reaction after 1 hr, give remaining 28u.

Premed each day:
Kytril 1mg + Dex 20mg + Ativan 1mg IV/30 min
Tylenol 650mg po q6h x 4 doses days 2,9,16.

Repeat q 3 wks.

Call Rx for Compazine

 

UNKNOWN PRIMARY

Nashville Regimen:

Taxol 200 mg/m2
Carboplatin AUC=6
Etoposide 50 mg/100 mg alternating daily x 10 days
Repeat q 3 weeks

RR = 47% CR=13%
MS = 13.4 months

 

PANCREAS: ADENOCARCINOMA

Single agent Gemcitabine

   Gem 1000 mg/m2 x 7 weeks, then 3/4 weeks

Irinotecan/Oxaliplatin (2nd line)

Irinotecan 60 mg/m2 days 1,8,15
Oxaliplatin 60 mg/m2 days 1,15

Given on a 4 week cycle

In advanced ca, pretreated patients, led to 20% benefit response with average duration of 7 months. 10% PR, 23% stable disease. MTP 4 months, MS 6 months. Italian study. Oncology 67:93, 2004.

Gem/CDDP
(MDACC thinks has higher RR and longer TTP. No difference in OS)

            Gem 600 mg/m2 over 1 hour, then
            CDDP 30 mg/m2

            Give biweekly (days 1,15 on 28 day cycle)

RFS 2000 (rubitecan)

NEOPLASTIC MENINGITIS

High dose methotrexate
Intrathecal: DepoCyt, methotrexate, Ara-C


HIGH DOSE METHOTREXATE
(JCO 16:1561, 4/98)

 

Treat two weeks apart. Repeat 4 weeks and 8 weeks after second dose.

 

1.  Hydrate and alkalinize urine by giving ½ or normal saline + 20 meq KCL + 1 amp NaHCO3 at 125 ml/hr.

2.  Check urine pH q 6h. When >= 7.0, may begin chemo.

3.  If urine pH < 7>0, give 1 amp NaHCO3.

4.  Premed: Zofran 10 mg IV

5.  Methotrexate 8 gm/m2 in 500 ml NS IV/4 hours

6.  At end of methotrexate give Compazine 10 mg po.

7.  Exactly 24 hrs after completion of methotrexate, begin leucovorin 25 mg IV q 6h x 4 doses, then 25 mg po q 6h until methotrexate level is < 5 x 10-8 mol/L (or < 0.05 umol/L). (See Methotrexate Levels)

8.  Starting 24 hrs after the methotrexate is given, get STAT methotrexate level q 24 hrs.

 

DEPOCYT

 

50 mg IT weeks 1,3,5,7,9,13.

(Can stop any time it appears patient is not responding. Treatment has continued up to 8 months in some studies.) RR=26-70%.

Long half life -> CSF levels for up to 14 days. Works as well as IT methotrexate, but easier because of less-frequent administration required.
Administration: Comes 50 mg/5ml. Agitate to resuspend solution. Inject slowly over 1-5 minutes. Patient should lie flat for 1 hour afterwards. Also start the patient on Decadron 4 mp po/IV BID days 1-5 each time (to reduce arachnoiditis). Modifications:  If any neurotoxicity, reduce to 25 mg.

 

METHOTREXATE

 

10 mg IT twice weekly x 4 weeks, then if responding, every week x 4, then every other week x 4. RR= 20%.

 

ARA-C

 

Ara-C 50 mg IT twice weekly x 4 weeks, then if responding, once a week x 4, then every other week x 4, then every 4 weeks x 4. RR=15%.

 

 

PROSTATE – Undifferentiated/Small Cell

(Proc ASCO 14:601, 1995. Frank, SJ)

 

Platinum plus Etoposide in PD prostate ca (with small cell or neuroendocrine features) and low PSA. 61% RR but considerable myelotoxicity.


Carbo AUC 5 or CDDP 70 mg/m2

Etop 120 mg/m2 IV x 3 days or 50 po BID x 14 days

Estramustine 10 mg/kg po QD

Given q 4wks x 1-6 cycles (med=4)

 

METASTATIC PROSTATE

 

   First line hormonal therapy

   Second line hormonal therapy

 

 

HEPATOCELLULAR CARCINOMA

 

5FU 200 mg/m2/day CIV x 21 days

IFN alpha 2b 4 MU/m2 SQ TIW

 

Repeat q28 days.

 

Yields 25% RR and MS 15.5 months in patients with unresectable disease.

Instead of 5FU can use Xeloda 1000-1250 mg/m2 BID x 14 days every 21 days.

 

DHAP

For relapsed or refractory aggressive NHL. (Blood 71(1):117-22, Jan 1988)

 

Cisplatin 100 mg/m2 continuous IV over 24 hours (with mannitol) day 1

Ara-C 2 gm/m2 IV bolus x 2 doses, 12 hours apart, day 2

Decadron 40 mg daily days 1-4

 

See ESHAP for cisplatin adjustment.

 

Given q 3-4 weeks x 6-10 cycles. Median patient age 55. 31% CR, 26% PR. Response usually noted after 2nd cycle. Overall 2YS 25%.

 

DICE

Ann Oncol 1991 Jan;2 Suppl 1:43-6

 

Decadron 10 mg q6h

Ifosfamide 1 gm/m2 (with Mesna)

Cisplatin 25 mg/m2

Etoposide 100 mg/m2

 

Give above daily x 4 days every 3-4 weeks.

27% CR, 50% PR (small study)

See ESHAP for cisplatin adjustment.

 

DHAX

Br J Haematol 2001 Dec;115(4):786-92

 

Like DHAP, but uses oxaliplatin instead of cisplatin

 

Oxaliplatin 130 mg/m2 day 1

Ara-C 2 gm/m2 IV bolus x 2 doses day 2

Decadron 40 mg days 1-4

 

Median patient age 58. 50% RR. Small study that included various types of NHL. Lack of renal toxicity is a plus prior to transplant.

 

ICE

J Clin Oncol 1999 Dec;17(12):3776-85 (MSKCC)

 

Substitutes carboplatin for cisplatin.

Need double-lumen catheter or 2 IVs

 

Etoposide 100 mg/m2 days 1-3

Carboplatin AUC 5 day 2 (with max of 800 mg)

Ifosfamide 5 gm/m2 continuous IV over 24 hours day 2

(Mesna 5 gm/m2 mixed with ifosfamide)

 

G-CSF 5 mcg/kg days 5-12

 

Ifosfamide given over 24 hours to reduce CNS adverse effects. There were no dose reductions; instead, treatment was delayed until the absolute neutrophil count was more than 1,000/uL and the platelet count was more than 50,000/uL.

 

ANAL CARCINOMA

 

Radiotherapy 4500 cGy in 25 fractions

5FU 1000 mg/m2/day CIV days 1-4

Mitomycin C 10 mg/m2 IV day 1

 

Repeat once in 4 weeks.

 

Remember that Mitomycin has late nadir of 4-6 weeks.

 

Biopsy again 4 weeks after RT completed. If negative, no further treatment. If positive, consider another 900 cGy in 5 fractions and

 

5FU 1000 mg/m2/day CIV days 1-4

CDDP 75-100 mg/m2 day 2.

 

If biopsy persistently positive, perform surgery (APR).