Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma

Michael B. Atkins, Kevin R. O'Boyle, Jeffrey A. Sosman, Geoffrey R. Weiss, Kim A. Margolin, Mary Lou Ernest, Kerry Kappler, James W. Mier, Joseph A. Sparano, Richard I. Fisher, John R. Eckardt, Cindy Pereira, Frederick R. Aronson

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. Patients and Methods: Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2, 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. Results: Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76% of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8%), and 13 achieved a partial response (PR). The overall objective response rate was 42% (95% confidence interval [CI], 26% to 58%). Six additional patients had greater than 50% tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. Conclusion: This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.

Original languageEnglish (US)
Pages (from-to)1553-1560
Number of pages8
JournalJournal of Clinical Oncology
Volume12
Issue number8
StatePublished - Aug 1994
Externally publishedYes

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Melanoma
Dacarbazine
Interleukin-2
Cisplatin
Tamoxifen
Drug Therapy
Platelet Transfusion
Neutropenia
Thrombocytopenia
Immunotherapy
Fatigue
Anemia
Weight Loss
Therapeutics
Confidence Intervals
Hemorrhage
Cytokines
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Atkins, M. B., O'Boyle, K. R., Sosman, J. A., Weiss, G. R., Margolin, K. A., Ernest, M. L., ... Aronson, F. R. (1994). Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. Journal of Clinical Oncology, 12(8), 1553-1560.

Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. / Atkins, Michael B.; O'Boyle, Kevin R.; Sosman, Jeffrey A.; Weiss, Geoffrey R.; Margolin, Kim A.; Ernest, Mary Lou; Kappler, Kerry; Mier, James W.; Sparano, Joseph A.; Fisher, Richard I.; Eckardt, John R.; Pereira, Cindy; Aronson, Frederick R.

In: Journal of Clinical Oncology, Vol. 12, No. 8, 08.1994, p. 1553-1560.

Research output: Contribution to journalArticle

Atkins, MB, O'Boyle, KR, Sosman, JA, Weiss, GR, Margolin, KA, Ernest, ML, Kappler, K, Mier, JW, Sparano, JA, Fisher, RI, Eckardt, JR, Pereira, C & Aronson, FR 1994, 'Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma', Journal of Clinical Oncology, vol. 12, no. 8, pp. 1553-1560.
Atkins MB, O'Boyle KR, Sosman JA, Weiss GR, Margolin KA, Ernest ML et al. Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. Journal of Clinical Oncology. 1994 Aug;12(8):1553-1560.
Atkins, Michael B. ; O'Boyle, Kevin R. ; Sosman, Jeffrey A. ; Weiss, Geoffrey R. ; Margolin, Kim A. ; Ernest, Mary Lou ; Kappler, Kerry ; Mier, James W. ; Sparano, Joseph A. ; Fisher, Richard I. ; Eckardt, John R. ; Pereira, Cindy ; Aronson, Frederick R. / Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 8. pp. 1553-1560.
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abstract = "Purpose: To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. Patients and Methods: Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2, 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. Results: Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76{\%} of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8{\%}), and 13 achieved a partial response (PR). The overall objective response rate was 42{\%} (95{\%} confidence interval [CI], 26{\%} to 58{\%}). Six additional patients had greater than 50{\%} tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. Conclusion: This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.",
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T1 - Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma

AU - Atkins, Michael B.

AU - O'Boyle, Kevin R.

AU - Sosman, Jeffrey A.

AU - Weiss, Geoffrey R.

AU - Margolin, Kim A.

AU - Ernest, Mary Lou

AU - Kappler, Kerry

AU - Mier, James W.

AU - Sparano, Joseph A.

AU - Fisher, Richard I.

AU - Eckardt, John R.

AU - Pereira, Cindy

AU - Aronson, Frederick R.

PY - 1994/8

Y1 - 1994/8

N2 - Purpose: To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. Patients and Methods: Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2, 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. Results: Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76% of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8%), and 13 achieved a partial response (PR). The overall objective response rate was 42% (95% confidence interval [CI], 26% to 58%). Six additional patients had greater than 50% tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. Conclusion: This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.

AB - Purpose: To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. Patients and Methods: Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2, 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. Results: Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76% of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8%), and 13 achieved a partial response (PR). The overall objective response rate was 42% (95% confidence interval [CI], 26% to 58%). Six additional patients had greater than 50% tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. Conclusion: This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.

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