A multicenter, multinational analysis of mitomycin C in refractory metastatic colorectal cancer

Ferrarotto, Renata; Machado, Karime; Mak, Milena P.; Shah, Neeraj; Takahashi, Tiago K.; Costa, Frederico P.; Overman, Michael J.; Kopetz, Scott; Hoff, Paulo M.

doi:10.1016/j.ejca.2012.01.008

« Previous Next »European Journal of Cancer
Volume 48, Issue 6 , Pages 820-826, April 2012

A multicenter, multinational analysis of mitomycin C in refractory metastatic colorectal cancer

Renata Ferrarotto
- Hospital Sírio Libanês, Clinical Oncology Department, Rua D. Adma Jafet 91, São Paulo, SP 01308-050, Brazil
- Tel.: +55 11 3155 8888.
- Corresponding author: Address: Rua D. Adma Jafet 91, 01308-050 Bela Vista, São Paulo, S.P, Brazil. Tel.: +55 11 3155 0995, mobile: +55 11 9453 5378; fax: +55 11 3155 0250.
Karime Machado
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr. Arnaldo 251, São Paulo, SP 01246-000, Brazil
- Tel.: +55 11 3893 2000.
Milena P. Mak
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr. Arnaldo 251, São Paulo, SP 01246-000, Brazil
- Tel.: +55 11 3893 2000.
Neeraj Shah
- University of Texas M.D. Anderson Cancer Center, Gastrointestinal Medical Oncology Department, 1515 Holcombe Blvd, Houston, TX 77030, United States
- Tel.: +1 877 632 6789.
Tiago K. Takahashi
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr. Arnaldo 251, São Paulo, SP 01246-000, Brazil
- Tel.: +55 11 3893 2000.
Frederico P. Costa
- Hospital Sírio Libanês, Clinical Oncology Department, Rua D. Adma Jafet 91, São Paulo, SP 01308-050, Brazil
- Tel.: +55 11 3155 8888.
Michael J. Overman
- University of Texas M.D. Anderson Cancer Center, Gastrointestinal Medical Oncology Department, 1515 Holcombe Blvd, Houston, TX 77030, United States
- Tel.: +1 877 632 6789.
Scott Kopetz
- University of Texas M.D. Anderson Cancer Center, Gastrointestinal Medical Oncology Department, 1515 Holcombe Blvd, Houston, TX 77030, United States
- Tel.: +1 877 632 6789.
Paulo M. Hoff
- Hospital Sírio Libanês, Clinical Oncology Department, Rua D. Adma Jafet 91, São Paulo, SP 01308-050, Brazil
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr. Arnaldo 251, São Paulo, SP 01246-000, Brazil
- Tel.: +55 11 3155 8888.
- Tel.: +55 11 3893 2000.

published online 13 February 2012.

Abstract

Background

A considerable number of metastatic colorectal cancer (mCRC) patients who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies, still have adequate performance status and desire further treatment. Mitomycin C (MMC) has been widely used in this context, and despite good tolerability, there are doubts regarding its true benefit.

Methods

In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated patients who received MMC as single agent or in combination for mCRC at three different institutions in two countries.

Results

Median patient’s age was 54years old, 57% were male and 94% had performance status ECOG 0 or 1. MMC was used in second line in 11%, third line in 38% and fourth line or beyond in 51% of patients. 58% received MMC combinations, mainly with capecitabine. Grade 3 or 4 toxicity was observed in 5% of patients and 6% required dose reductions. Median time to treatment failure (TTF) was 1.7months with MMC and 3.6months on the regimen prior to MMC, with a ratio between these TTF below 1 in 82% of patients. Median survival was only 4.5months (95% confidence interval (CI) of 3.48–5.56).

Conclusions

This retrospective data represent the largest reported series of unselected refractory mCRC patients treated with MMC. The median survival of 4.5months is similar to the survival expected for best supportive care. This lack of activity strongly suggests that MMC should not be routinely used in refractory mCRC.

Keywords: Mitomycin C, Metastatic colorectal cancer, Refractory setting