GEMOX Active With Low Toxicity in Pancreatic Cancer

SAN FRANCISCO—In patients with advanced pancreatic cancer, the combination of gemcitabine (Gemzar) followed by oxaliplatin (investigational in the United States) (GEMOX) is active with low toxicity, Christophe Louvet, MD, Hôpital St-Antoine, Paris, France, said at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 506).

The rationale for the gemcitabine/oxaliplatin combination is that the two agents have distinctly different mechanisms of action and patterns of resistance without overlapping toxicities.

Preclinical investigations looking into the possible combined effects of gemcitabine/oxaliplatin or gemcitabine/cisplatin (Platinol) found the best synergy effects for the sequence of gemcitabine followed by oxaliplatin, Dr. Louvet said.

The current phase II trial included 64 patients (mean age, 59.5 years) treated at eight centers; 47% had stage II-III locally advanced disease and 53% had stage IV metastatic disease. Enrollment criteria included Karnofsky performance status of 60 to 100.

The Regimen

Patients received gemcitabine 1,000 mg/m² in a 10 mg/m²/min infusion on day 1 and oxaliplatin 100 mg/m² in a 2-hour infusion on day 2. Treatment was repeated every 2 weeks for six cycles followed by chemoradiation with fluorouracil in locally advanced patients, or until progression of disease in metastatic patients.

Partial responses were reported in 19 patients, stable disease in 28, and progressive disease in 16, for a response rate of 30.2%. Response rates for locally advanced patients (31%) and metastatic disease patients (30.3%) were similar. The clinical benefit response rate was 39.7% (23 of 58 patients), Dr. Louvet said.

Among the 30 locally advanced patients, radiation at 55 Gy over 5 weeks (45 Gy plus a 10-Gy boost) was given to 12 patients whose disease had been controlled with GEMOX. Among 6 other well-controlled patients, investigators chose not do administer chemoradiation. The remaining 12 (40%) had metastatic progression within the first six GEMOX cycles.

Survival Results

At a median follow-up of 13 months, median progression-free survival was 5.3 months for all patients, 6.2 months for locally advanced patients, and 4.1 months for metastatic patients.

Overall survival at 1-year was 35.8% for all patients, 46.9% for locally advanced patients, and 25% for metastatic disease patients. Median survival was 9.2 months for all patients, 11.5 for locally advanced patients, and 8.7 for metastatic disease patients.

Dr. Louvet noted that the GEMOX regimen was "quite well tolerated." Through 574 evaluable cycles (median, 9 cycles), grade 3-4 toxicities were few at 1.7% per cycle for neutropenia, 1.3% for thrombocytopenia, 2% for nausea-vomiting, 0% for mucositis, and 1.6% for diarrhea. Grade 1-2 toxicities were experienced by 65.7% of patients. There were only two cases overall (3.1%) of grade 2 alopecia. Oxaliplatin was discontinued (after 8 to 15 cycles) in seven patients (10.9%) because of grade 3 peripheral neuropathy.

Dr. Louvet concluded: "The GEMOX combination is active in advanced pancreatic adenocarcinoma. The remarkable low toxicity is of major value in this palliative situation."

He noted further that the GEMOX combination is being evaluated against standard treatment in a GERCOR phase III trial (opened in March 2001) with survival as the primary endpoint.

ECOG Study

Dr. Louvet said that an Eastern Cooperative Oncology Group (ECOG) phase III trial will assess the respective contributions of oxaliplatin and gemcitabine at a constant infusion rate.