A Dose Escalation Study of Gemcitabine plus Pemetrexed Administered Biweekly in Patients with Solid Tumors

Abstract

Purpose: The study aimed to determine the maximum tolerated doses (MTDs) and identify the dose-limiting toxicities of the biweekly administration of pemetrexed plus gemcitabine in patients with solid tumors. Patients and Methods: Patients with advanced malignancies were treated with escalated doses of gemcitabine and pemetrexed (starting doses 1,250 and 300 mg/m², respectively) both given on days 1 and 15 in cycles of 4 weeks. Results: Forty-one patients were treated at 7 dose levels. The MTD was reached at the dose of 1,750 mg/m² for gemcitabine and 450 mg/m² for pemetrexed. Dose-limiting events were grade IV neutropenia, febrile neutropenia and treatment delay due to grade III hematological toxicities. One partial response in a pretreated patient with ovarian cancer was observed, while 4 other patients experienced stable disease. Conclusions: The biweekly administration of gemcitabine plus pemetrexed at the recommended MTDs is safe, well tolerated and demonstrates antitumor activity which merits further evaluation in phase II studies.

A Phase I Trial of Pemetrexed Plus Gemcitabine Given Biweekly with B-Vitamin Support in Solid Tumor Malignancies or Advanced Epithelial Ovarian Cancer

“…Sixty-six percent of patients had received two or more chemotherapy regimens before enrollment. The MTD in that trial was gemcitabine 1,750 mg/m 2 plus pemetrexed 450 mg/m 2 , with DLTs related to myelosuppression (13). These results are consistent with the MTDs and toxicity profiles defined in solid tumor and the ovarian cancer cohorts treated in the phase I study reported here.…”

Pemetrexed Improves Tumor Selectivity of 111In-DTPA-Folate in Mice with Folate Receptor–Positive Ovarian Cancer

“…PMX is approved by the Food and Drug Administration for the treatment of malignant mesothelioma in combination with cisplatin and as a single agent for the treatment of non-small cell lung cancer (18). Moreover, encouraging results were obtained in diverse clinical studies with PMX alone or in combination with other chemotherapeutics (e.g., gemcitabine) to treat a wide range of malignancies (e.g., carcinomas of the ovary, breast, colorectum, head and neck, uterine cervix, and so forth) (18,(24)(25)(26)(27). As structural analogs of folic acid, antifolates use the same transporters to gain entry into the cell interior.…”

Pemetrexed and Gemcitabine for Biliary Tract and Gallbladder Carcinomas: a North Central Cancer Treatment Group (NCCTG) Phase I and II Trial, N9943

“…The dose established in this trial was lower than that established in a separate phase I trial for patients with solid tumors [27]. In that phase I trial, an MTD of pemetrexed 450 mg/m 2 and gemcitabine 1,750 mg/m 2 on days 1 and 15 was reached.…”