Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies

George Somlo, Warren Chow, Victor Hamasaki, Lucille Leong, Kim Margolin, Robert Morgan, Irena Sniecinski, Paul Frankel, Debbie Reardon, Jeff Longmate, James Raschko, Stephen Shibata, Margaret O'Donnell, Eileen Smith, Merry Tetef, Stephen Forman, Yun Yen, Arturo Molina, James H. Doroshow

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). Fifty patients with high-risk primary (n=17) or stage IV breast cancer (n=29) or other malignancies (n=4) received 2 cycles of intravenous melphalan, 20 to 151.8 mg/m2, and cisplatin, 200 mg/m2, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF. Starting at 40 mg/m2 of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m2 per cycle. There were no treatment-related deaths. Cycle 2 was delivered at a median of 1.7 months after cycle 1; 72% of patients treated at the MTD received both cycles. Cycle 2 was omitted when patients refused it or had disease progression or toxicities, primarily prolonged thrombocytopenia. Complete response rates in stage IV breast cancer patients increased from 28% pre-HDCT to 55% after cycle 2. At a median follow-up of 4.6 years (range, 1.5-8.1 years), 11 of 29 patients with stage IV breast carcinoma were alive with 5-year projected progression-free and overall survival rates of 19% (95% confidence interval [CI], 7%-41%) and 39% (95% CI, 20%-62%), respectively. Five-year projected progression-free and overall survival rates for patients with stage IV breast cancer in complete response following HDCT versus all others were 35% (95% CI, 15%-70%) versus 0% (P = .01) and 61% (95% CI, 35%-91%) versus 10% (95% CI, 2%-60%) (P = .003; log-rank test), respectively. Estrogen-receptor positivity was predictive of reduced risk of progression (relative risk [RR], 0.25; 95% CI, 0.10-0.65; P = .003) and death (RR, 0.27; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-year projected relapse-free and overall survival rates were 71% (95% CI, 43%-96%) and 82% (95% CI, 56%-100%), respectively, for the 17 patients with high-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplatin with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.

Original languageEnglish
Pages (from-to)284-293
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume7
Issue number5
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

Fingerprint

Melphalan
Cisplatin
Blood Cells
Stem Cells
Confidence Intervals
Breast Neoplasms
Neoplasms
Maximum Tolerated Dose
Survival Rate
Drug Therapy
Disease-Free Survival
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Thrombocytopenia
Estrogen Receptors
Disease Progression
Blood Platelets
Recurrence

Keywords

  • Breast cancer
  • Cisplatin
  • High-dose chemotherapy
  • Melphalan
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies. / Somlo, George; Chow, Warren; Hamasaki, Victor; Leong, Lucille; Margolin, Kim; Morgan, Robert; Sniecinski, Irena; Frankel, Paul; Reardon, Debbie; Longmate, Jeff; Raschko, James; Shibata, Stephen; O'Donnell, Margaret; Smith, Eileen; Tetef, Merry; Forman, Stephen; Yen, Yun; Molina, Arturo; Doroshow, James H.

In: Biology of Blood and Marrow Transplantation, Vol. 7, No. 5, 01.01.2001, p. 284-293.

Research output: Contribution to journalArticle

Somlo, G, Chow, W, Hamasaki, V, Leong, L, Margolin, K, Morgan, R, Sniecinski, I, Frankel, P, Reardon, D, Longmate, J, Raschko, J, Shibata, S, O'Donnell, M, Smith, E, Tetef, M, Forman, S, Yen, Y, Molina, A & Doroshow, JH 2001, 'Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies', Biology of Blood and Marrow Transplantation, vol. 7, no. 5, pp. 284-293. https://doi.org/10.1053/bbmt.2001.v7.pm11400951
Somlo, George ; Chow, Warren ; Hamasaki, Victor ; Leong, Lucille ; Margolin, Kim ; Morgan, Robert ; Sniecinski, Irena ; Frankel, Paul ; Reardon, Debbie ; Longmate, Jeff ; Raschko, James ; Shibata, Stephen ; O'Donnell, Margaret ; Smith, Eileen ; Tetef, Merry ; Forman, Stephen ; Yen, Yun ; Molina, Arturo ; Doroshow, James H. / Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies. In: Biology of Blood and Marrow Transplantation. 2001 ; Vol. 7, No. 5. pp. 284-293.
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AU - Somlo, George

AU - Chow, Warren

AU - Hamasaki, Victor

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AU - Margolin, Kim

AU - Morgan, Robert

AU - Sniecinski, Irena

AU - Frankel, Paul

AU - Reardon, Debbie

AU - Longmate, Jeff

AU - Raschko, James

AU - Shibata, Stephen

AU - O'Donnell, Margaret

AU - Smith, Eileen

AU - Tetef, Merry

AU - Forman, Stephen

AU - Yen, Yun

AU - Molina, Arturo

AU - Doroshow, James H.

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N2 - We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). Fifty patients with high-risk primary (n=17) or stage IV breast cancer (n=29) or other malignancies (n=4) received 2 cycles of intravenous melphalan, 20 to 151.8 mg/m2, and cisplatin, 200 mg/m2, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF. Starting at 40 mg/m2 of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m2 per cycle. There were no treatment-related deaths. Cycle 2 was delivered at a median of 1.7 months after cycle 1; 72% of patients treated at the MTD received both cycles. Cycle 2 was omitted when patients refused it or had disease progression or toxicities, primarily prolonged thrombocytopenia. Complete response rates in stage IV breast cancer patients increased from 28% pre-HDCT to 55% after cycle 2. At a median follow-up of 4.6 years (range, 1.5-8.1 years), 11 of 29 patients with stage IV breast carcinoma were alive with 5-year projected progression-free and overall survival rates of 19% (95% confidence interval [CI], 7%-41%) and 39% (95% CI, 20%-62%), respectively. Five-year projected progression-free and overall survival rates for patients with stage IV breast cancer in complete response following HDCT versus all others were 35% (95% CI, 15%-70%) versus 0% (P = .01) and 61% (95% CI, 35%-91%) versus 10% (95% CI, 2%-60%) (P = .003; log-rank test), respectively. Estrogen-receptor positivity was predictive of reduced risk of progression (relative risk [RR], 0.25; 95% CI, 0.10-0.65; P = .003) and death (RR, 0.27; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-year projected relapse-free and overall survival rates were 71% (95% CI, 43%-96%) and 82% (95% CI, 56%-100%), respectively, for the 17 patients with high-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplatin with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.

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KW - Cisplatin

KW - High-dose chemotherapy

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KW - Stem cell transplantation

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