Once metastatic breast cancer patients fail anthracyclines or taxanes, physicians have very limited options for further treatment. One available drug is capecitabine, which is approved in the United States for treatment of refractory metastatic breast cancer. Capecitabine can be effective, but has a number of associated toxicities, such as hand-foot syndrome.

Thus, there is a need to identify new, effective anti-tumor agents for the treatment of metastatic breast cancer refractory to anthracyclines or taxanes. One such agent is the topoisomerase I inhibitor irinotecan. In breast cancer models, irinotecan showed evidence of pre-clinical activity. In addition, a few small Japanese clinical investigations suggested that irinotecan could be useful in metastatic breast cancer.

Dr. Perez and colleagues with the North Central Cancer Treatment Group (NCCTG) have performed a randomized, phase II study to further clarify the potential of irinotecan in metastatic breast cancer.

This study included 102 metastatic breast cancer patients who had received at most 1 adjuvant chemotherapy regimen, and up to 2 prior regimens for metastatic disease. At least one of the prior regimens had to be an anthracycline or taxane.

Many of the patients had received 2 or 3 prior chemotherapy regimens (55% for the weekly regimen and 73% for the every 3 weeks regimen), and many had received both anthracyclines and taxanes (58% and 63%, respectively, of the weekly and every 3 weeks groups).

In the first study arm, patients received 6-week cycles of weekly irinotecan (100 mg/m² weekly for 4 weeks and a 2 week rest). In the second study arm, they received a higher dose less frequently (240 mg/m² every 3 weeks).

As of ASCO, about half the patients were evaluable for toxicity. The most common grade 3-4 toxicity was neutropenia, occurring in 32% of patients in the weekly irinotecan group and 36% in the every 3 weeks group. Grade 3 febrile neutropenia occurred in 4% of the weekly group and 6% of the second group; there was no grade 4 febrile neutropenia.

Dr. Perez presented response rates for all 102 patients in the study. Response rates ranged from 15% to 18% for patients who received either prior anthracycline or prior taxane. Interestingly, of the patients who had received both an anthracycline and taxane, investigators reported a response rate of 27% (8 of 30 patients) for the 30 randomized to the weekly irinotecan arm and 13% for those randomized to irinotecan every 3 weeks.

If these results are confirmed in phase III trials, physicians may have a new treatment option for refractory metastatic breast cancer that provides a good response rate with only limited toxicity compared with other options.

Dr. Perez and colleagues are planning a randomized phase III trial comparing 3 arms: sequential irinotecan then capecitabine, sequential capecitabine then irinotecan, or a combination of both drugs.

(abstract #206)