Combination pemetrexed, gemcitabine too toxic for use in advanced urothelial cancer, study data suggest

Combination pemetrexed disodium and gemcitabine may have moderate antitumor activity in treatment-naive patients with advanced urothelial cancer, but at the price of significant myelosuppression that makes the combination undesirable, study data suggest.

Gemcitabine and pemetrexed both have broad antitumor activity and potential use in patients with compromised renal function, according to the authors of the study.

These characteristics, along with promising...

Combination pemetrexed disodium and gemcitabine may have moderate antitumor activity in treatment-naive patients with advanced urothelial cancer, but at the price of significant myelosuppression that makes the combination undesirable, study data suggest.

Gemcitabine and pemetrexed both have broad antitumor activity and potential use in patients with compromised renal function, according to the authors of the study.

These characteristics, along with promising preclinical and single-agent data, led researchers to conduct a Phase II trial in which 46 treatment-naive patients with confirmed transitional cell carcinoma of the urothelium with evidence of progressive, bidimensionally measurable, regional or metastatic disease were administered pemetrexed disodium 500 mg/m2 of body surface area and gemcitabine 1,000 mg/m2 on day 1, with gencitabine repeated on day 8. This cycle was repeated every 3 weeks for a maximum of 6 cycles.

Overall, 27% of patients withdrew from therapy because of progressive disease, 23% withdrew because of excess toxicity, and 39% completed all 6 cycles of therapy. Forty of 44 patients needed at least 1 change to their therapy regimen, the authors noted.

Of the 38 patients assessable for response, 2 patients achieved a complete response and 12 patients achieved a partial response, for an overall response rate of 31.8% (90% CI, 20.4%-45.2%). At the time of the present analysis, 34 patients (77%) had progressed, while 6 patients (14%) were alive and progression free. This translated into a median time to progression of 5.8 months (95% CI, 3 months-7.7 months) and medial overall survival of 13.4 months (95% CI, 8.8 months-16.1 months).

There were 2 deaths due to toxicity, including 1 due to febrile neutropenia-related sepsis and 1 due to infection in a nonneutropenic setting. Additionally, 33 patients (75%) experienced serious neutropenia, 5 patients (11%) experienced febrile neutropenia, 3 patients (7%) experienced grade III thrombocytopenia, and 6 patients (14%) experienced grade III anemia.

"The combination of pemetrexed and gemcitabine has activity in advanced urothelial cancer, but at a significant cost in terms of toxicity," the authors concluded. "Further development of this doublet in urothelial cancer seems unwarranted."

These findings were published online May 5 ahead of print in the journal Cancer by Dreicer R, et al.

This information concerns a use that has not been approved by the Food and Drug Administration.