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

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6207-6212
Number of pages6
JournalJournal of Clinical Oncology
Volume27
Issue number36
DOIs
StatePublished - Dec 20 2009

Fingerprint

Biological Therapy
Multicenter Studies
Melanoma
Maintenance
Survival
Disease-Free Survival
Interleukin-2
interferon alfa-2b
Granulocyte-Macrophage Colony-Stimulating Factor
Neoplasm Metastasis
Drug Therapy
Dacarbazine
Vinblastine
Cisplatin
Disease Progression
Survival Rate
Randomized Controlled Trials
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

O'Day, S. J., Atkins, M. B., Boasberg, P., Wang, H. J., Thompson, J. A., Anderson, C. M., ... Weber, J. S. (2009). Phase II multicenter trial of maintenance biotherapy after induction concurrent biochemotherapy for patients with metastatic melanoma. Journal of Clinical Oncology, 27(36), 6207-6212. https://doi.org/10.1200/JCO.2008.20.3075

Phase II multicenter trial of maintenance biotherapy after induction concurrent biochemotherapy for patients with metastatic melanoma. / O'Day, Steven J.; Atkins, Michael B.; Boasberg, Peter; Wang, He Jing; Thompson, John A.; Anderson, Clay M.; Gonzalez, Rene; Lutzky, Jose; Amatruda, Thomas; Hersh, Evan M; Weber, Jeffrey S.

In: Journal of Clinical Oncology, Vol. 27, No. 36, 20.12.2009, p. 6207-6212.

Research output: Contribution to journalArticle

O'Day, SJ, Atkins, MB, Boasberg, P, Wang, HJ, Thompson, JA, Anderson, CM, Gonzalez, R, Lutzky, J, Amatruda, T, Hersh, EM & Weber, JS 2009, 'Phase II multicenter trial of maintenance biotherapy after induction concurrent biochemotherapy for patients with metastatic melanoma', Journal of Clinical Oncology, vol. 27, no. 36, pp. 6207-6212. https://doi.org/10.1200/JCO.2008.20.3075
O'Day, Steven J. ; Atkins, Michael B. ; Boasberg, Peter ; Wang, He Jing ; Thompson, John A. ; Anderson, Clay M. ; Gonzalez, Rene ; Lutzky, Jose ; Amatruda, Thomas ; Hersh, Evan M ; Weber, Jeffrey S. / Phase II multicenter trial of maintenance biotherapy after induction concurrent biochemotherapy for patients with metastatic melanoma. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 36. pp. 6207-6212.
@article{f065e0a8716845bfb66b82d7ee33a5ec,
title = "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-na{\"i}ve 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.",
author = "O'Day, {Steven J.} and Atkins, {Michael B.} and Peter Boasberg and Wang, {He Jing} and Thompson, {John A.} and Anderson, {Clay M.} and Rene Gonzalez and Jose Lutzky and Thomas Amatruda and Hersh, {Evan M} and Weber, {Jeffrey S.}",
year = "2009",
month = "12",
day = "20",
doi = "10.1200/JCO.2008.20.3075",
language = "English (US)",
volume = "27",
pages = "6207--6212",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "36",

}

TY - JOUR

T1 - Phase II multicenter trial of maintenance biotherapy after induction concurrent biochemotherapy for patients with metastatic melanoma

AU - O'Day, Steven J.

AU - Atkins, Michael B.

AU - Boasberg, Peter

AU - Wang, He Jing

AU - Thompson, John A.

AU - Anderson, Clay M.

AU - Gonzalez, Rene

AU - Lutzky, Jose

AU - Amatruda, Thomas

AU - Hersh, Evan M

AU - Weber, Jeffrey S.

PY - 2009/12/20

Y1 - 2009/12/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=74949089360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74949089360&partnerID=8YFLogxK

U2 - 10.1200/JCO.2008.20.3075

DO - 10.1200/JCO.2008.20.3075

M3 - Article

C2 - 19917850

AN - SCOPUS:74949089360

VL - 27

SP - 6207

EP - 6212

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 36

ER -