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There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration. This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0–2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m2 intravenously (IV) and irinotecan 50 mg/m2 IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning. A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31–79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy. Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens. [ABSTRACT FROM AUTHOR]

For nearly 40 years, the medical treatment of colorectal cancer had been limited to the fluoropyrimidines until the recent development of irinotecan (CPT-11). In the past decade, a new agent has appeared, oxaliplatin. This third-generation platinum compound has synergistic activity with 5-fluorouracil and is non-cross-resistant with 5-fluorouracil, CPT-11, and other platinum agents. Numerous clinical trials in Europe have demonstrated the activity of oxaliplatin in patients with untreated and refractory metastatic colorectal cancer. Nevertheless, the US Food and Drug Administration recently denied approval for oxaliplatin as first-line treatment of colorectal cancer because of a lack of clear-cut survival advantage in clinical trials. Additional clinical trials in patients with colorectal cancer are ongoing in the United States and will test the activity of oxaliplatin in the metastatic and adjuvant setting. These studies will define the role for what appears to be a very useful and important agent. [ABSTRACT FROM AUTHOR]

Purpose: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy. Methods: PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed. Results: No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1–6). Toxicity included neutropenia and neurologic side-effects, which were ≥ grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P=0.04). Conclusions: PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity. [ABSTRACT FROM AUTHOR]