Phase II study of sequentially administered low-dose mitomycin-C (MMC) and irinotecan (CPT-11) in women with metastatic breast cancer (MBC)

Annals of Oncology : Official Journal of the European Society for Medical Oncology
E MrozekC L Shapiro

Abstract

Preclinical studies show that mitomycin-C (MMC) followed by irinotecan (CPT-11) is synergistic. Therefore, we evaluated the toxicity and efficacy of sequentially administered low-dose MMC and CPT-11 in patients (pts) with pretreated metastatic breast cancer (MBC). Secondary objective was to evaluate the correlation between MMC-induced topoisomerase I (TOPO I) expression and NAD(P)H:quinone oxireductase 1 (NQO1) genotypes in peripheral blood mononuclear cells (PBMC) and efficacy or toxicity of the regimen. Thirty-two pts received MMC i.v. 6 mg/m(2) day 1 and CPT-11 i.v. 125 mg/m(2) days 2 and 8 every 28 days for maximum of six cycles. TOPO I expression and NQO1 reductase genotyping in 23 of 32 (72%) pts were assayed by PCR. The median time to progression (TTP) was 4.7 months (95% confidence interval 4.0-5.4 months). TOPO I expression was increased 5- to 10-fold and 20- to 30-fold in PBMC at 24 and 168 h, respectively. There was no relationship between these markers and efficacy or toxicity of the regimen. Sequential low-dose MMC and CPT-11 was active and tolerable by pretreated MBC pts. Future trials should focus on less pretreated MBC pts and sequential tumor biopsies to test the hypothesis that increased intratumoral expressio...Continue Reading

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Citations

Jun 10, 2009·Cancer Chemotherapy and Pharmacology·Nse NtukidemTanios Bekaii-Saab
Dec 17, 2009·Cancer Chemotherapy and Pharmacology·Kathryn E ReinickeMatthew M Ames
Mar 21, 2013·Breast Cancer Research and Treatment·Iben KümlerDorte L Nielsen
Feb 18, 2012·Pharmacogenetics and Genomics·Galina KislukhinAnthony D Long
Nov 13, 2012·Annual Review of Pharmacology and Toxicology·Jane P F Bai, Darrell R Abernethy
May 6, 2014·Archives of Toxicology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Jan 22, 2013·Anales de pediatría : publicación oficial de la Asociación Española de Pediatría (A.E.P.)·C Hernández-MarquésL Madero Lopez

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