Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group.

Abstract

PURPOSE:

High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective.

PATIENTS AND METHODS:

S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS).

RESULTS:

In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms.

CONCLUSION:

Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.

• Authors: Lawrence E Flaherty, Megan Othus, Michael B Atkins, Ralph J Tuthill, John A Thompson, John T Vetto, Frank G Haluska, Alberto S Pappo, Jeffrey A Sosman, Bruce G Redman, James Moon, Antoni Ribas, John M Kirkwood, Vernon K Sondak
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 33 Pg. 3771-8 (Nov 20 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25332243 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Interferon alpha-2
• Interferon-alpha
• Interleukin-2
• Recombinant Proteins
• Vinblastine
• Dacarbazine
• Interferons
• Cisplatin

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Child
• Cisplatin (administration & dosage, adverse effects)
• Dacarbazine (administration & dosage, adverse effects)
• Female
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects, therapeutic use)
• Interferons (administration & dosage, adverse effects)
• Interleukin-2 (administration & dosage, adverse effects)
• Male
• Melanoma (drug therapy, mortality)
• Middle Aged
• Recombinant Proteins (adverse effects, therapeutic use)
• Vinblastine (administration & dosage, adverse effects)