Affiliation:
1. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
2. Santa Maria delle Croci Hospital, Ravenna, Italy
3. Cooperative Outcome Research (CORE)-Cineca, Bologna, Italy
Abstract
Abstract
Lessons Learned
Difficulties in translating in vitro results into clinical practice are inevitable. Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged.
Background
We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine. This combination was then advanced to a phase II clinical trial.
Methods
Patients with metastatic colorectal cancer in progression after standard treatment were included in the study. Adequate bone marrow reserve, normal hepatic and renal function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 were required. Treatment consisted of an 8-hour intravenous infusion of pemetrexed 150 mg/m2 on day 1 and a 30-minute intravenous infusion of gemcitabine 1,000 mg/m2 on day 3 of each cycle, repeated every 14 days.
Results
Fourteen patients were enrolled onto the study (first step). No objective responses were seen, and evidence of stable disease was observed in only one of the 12 evaluable patients. The most important grade 3–4 side effects were hematological toxicity (neutropenia 64.2%, thrombocytopenia 71.4%, anemia 28.7%), fatigue (50.0%), and stomatitis (21.5%). Median overall survival and time to progression were 5.8 months (95% confidence interval [CI]: 3.9–7.1) and 2.1 months (95% CI: 1.7–2.8), respectively.
Conclusion
The experimental pemetrexed-gemcitabine combination proved to be inactive and moderately toxic.
Publisher
Oxford University Press (OUP)
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