Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial.
OBJECTIVE
The addition of cytokines to chemotherapy has produced encouraging results in advanced melanoma. In this phase III trial, we compared the effects of chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon alfa-2b.


METHODS
Metastatic melanoma patients who had not previously received chemotherapy were stratified by prognostic factors and given chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was assessed every 6 weeks.


RESULTS
Among 190 patients enrolled, 91 were assessable for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were alive a median of 52 months from start of therapy. Response rates were 48% for biochemotherapy and 25% for chemotherapy (P =.001); six patients given biochemotherapy and two given chemotherapy had complete responses. Median time to progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for chemotherapy (P =.008); median survival was 11.9 and 9.2 months, respectively (P =.06). The influence of treatment on TTP and survival was confirmed in multivariate analyses with other prognostic factors not included in the original stratification. Biochemotherapy produced substantially more constitutional, hemodynamic, and myelosuppressive toxic effects.


CONCLUSIONS
Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.
Eton
Omar
O
Department Melanoma/Sarcoma, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. oeton@mdanderson.org
Legha
Sewa S
SS
Bedikian
Agop Y
AY
Lee
J Jack
JJ
Buzaid
Antonio C
AC
Hodges
Cynthia
C
Ring
Sigrid E
SE
Papadopoulos
Nicholas E
NE
Plager
Carl
C
East
Mary Jo
MJ
Zhan
Feng
F
Benjamin
Robert S
RS
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage
D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin