Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma.

Abstract

PURPOSE:

Biochemotherapy improves responses in metastatic melanoma, but not overall survival, in randomized trials. We developed a maintenance biotherapy regimen after induction biochemotherapy in an attempt to improve durability of responses and overall survival.

PATIENTS AND METHODS:

One hundred thirty-three chemotherapy-naïve patients with metastatic melanoma without CNS metastases were treated at 10 melanoma centers. The biochemotherapy induction regimen included cisplatin, vinblastine, dacarbazine, decrescendo interleukin-2 (IL-2), and interferon alfa-2b with granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine support. Patients not experiencing disease progression were eligible for maintenance biotherapy with low-dose IL-2 and GM-CSF followed by intermittent pulses of decrescendo IL-2 over 12 months. Patients were observed for response, progression-free survival, toxicity, and overall survival.

RESULTS:

The response rate to induction biochemotherapy was 44% (95% CI, 35% to 52%; complete response, 8%; partial response, 36%; stable disease, 29%). The median number of biochemotherapy cycles was four, and the median number of maintenance biotherapy cycles was five. The median progression-free survival was 9 months, and the median survival was 13.5 months. The 12-month and 24-month survival rates were 57% and 23%, respectively. Twenty percent of patients remain alive (12 without disease), with median follow-up of 30 months (95% CI, 25+ to 45+ months). Thirty-nine percent of patients developed CNS metastases. The median times to CNS progression and death were 8 months and 5 months, respectively.

CONCLUSION:

Maintenance biotherapy after induction biochemotherapy seems to prolong progression-free survival and improve overall survival compared with recent multicenter trials of biochemotherapy or chemotherapy. The regimen should be studied in a randomized clinical trial in patients with advanced metastatic melanoma. CNS progression remains a formidable challenge.

• Authors: Steven J O'Day, Michael B Atkins, Peter Boasberg, He-Jing Wang, John A Thompson, Clay M Anderson, Rene Gonzalez, Jose Lutzky, Thomas Amatruda, Evan M Hersh, Jeffrey S Weber
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 36 Pg. 6207-12 (Dec 20 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19917850 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-2
• Vinblastine
• Dacarbazine
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cisplatin

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cisplatin (administration & dosage)
• Dacarbazine (administration & dosage)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage)
• Humans
• Interleukin-2 (administration & dosage)
• Male
• Melanoma (drug therapy, pathology, secondary)
• Middle Aged
• Neoplasm Metastasis
• Remission Induction
• Skin Neoplasms (drug therapy, pathology, secondary)
• Survival Analysis
• Vinblastine (administration & dosage)
• Young Adult