A randomized phase III trial of biochemotherapy versus interferon-alpha-2b for adjuvant therapy in patients at high risk for melanoma recurrence.
The objective of this study was to compare the clinical benefit of biochemotherapy and interferon-alpha-2b (IFN) as adjuvant therapy. Biochemotherapy has higher response rates than other regimens in patients with metastatic melanoma. We conducted a randomized phase III study comparing the clinical benefit of biochemotherapy and IFN as adjuvant therapy. Patients who had undergone lymphadenectomy for melanoma metastatic to regional lymph nodes were randomly assigned to either biochemotherapy or IFN, and IFN patients were further randomized to either high-dose IFN (HDI) or intermediate-dose IFN (IDI). The primary end point was relapse-free survival (RFS); the secondary end point was overall survival (OS). The planned enrollment was 200 patients, the number required to have 80% power to detect, at a significance level of 5%, an improvement in median RFS from 18 to 36 months and an improvement in median OS from 40 to 80 months between the IFN and biochemotherapy groups. A futility analysis was performed because of slow accrual. One hundred and thirty-eight patients were enrolled - 71 in the biochemotherapy group, 34 in the HDI subgroup, and 33 in the IDI subgroup. No significant differences in median RFS or OS between the HDI and IDI subgroups were observed. With a median follow-up of 49.3 months, neither the biochemotherapy nor IFN group had reached median RFS or OS, and there were no significant differences in estimated median RFS or OS (P=0.86 and 0.45, respectively) between the two groups. Biochemotherapy is not more effective than IFN as adjuvant therapy for melanoma. These findings support early termination of this trial.
Department of Melanoma Medical Oncology, M. D. Anderson Cancer Center, The University of Texas, Houston 77030, Texas, USA.
Kevin B
KB
Kim
Sewa S
SS
Legha
Rene
R
Gonzalez
Clay M
CM
Anderson
Marcella M
MM
Johnson
Ping
P
Liu
Nicholas E
NE
Papadopoulos
Omar
O
Eton
Carl
C
Plager
Antonio C
AC
Buzaid
Victor G
VG
Prieto
Wen-Jen
WJ
Hwu
Angela M
AM
Frost
Gladys
G
Alvarado
Patrick
P
Hwu
Merrick I
MI
Ross
Jeffrey E
JE
Gershenwald
Jeffrey E
JE
Lee
Paul F
PF
Mansfield
Robert S
RS
Benjamin
Agop Y
AY
Bedikian
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin