Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma.
OBJECTIVE
Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen.


METHODS
Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days.


RESULTS
The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths.


CONCLUSIONS
The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.
O'Day
S J
SJ
Division of Medical and Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. o'days@jwci.org
Gammon
G
G
Boasberg
P D
PD
Martin
M A
MA
Kristedja
T S
TS
Guo
M
M
Stern
S
S
Edwards
S
S
Fournier
P
P
Weisberg
M
M
Cannon
M
M
Fawzy
N W
NW
Johnson
T D
TD
Essner
R
R
Foshag
L J
LJ
Morton
D L
DL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010865:Pilot Projects; D012871:Skin Diseases / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D007376:Interleukin-2; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin