A descriptive subgroup analysis demonstrated that the improvement in DFS for the ELOXATIN combination armcompared to the infusional 5-FU/LV alone armappeared to be maintained across genders. The effect of ELOXATIN on disease free survival benefit in patients ≥ 65 years of age was not conclusive. Insufficient subgroup sizes prevented analysis by race.

Combination Therapy with ELOXATIN and 5-FU/LV in Patients Previously Untreated for Advanced Colorectal Cancer

A North American, multicenter, open-label, randomized controlled study was sponsored by the National Cancer Institute (NCI) as an intergroup study led by the North Central Cancer Treatment Group (NCCTG). The study had 7 arms at different times during its conduct, four of which were closed due to either changes in the standard of care, toxicity, or simplification. During the study, the control armwas changed to irinotecan plus 5-FU/LV. The results reported below compared the efficacy and safety of two experimental regimens, ELOXATIN in combination with infusional 5-FU/LV and a combination of ELOXATIN plus irinotecan, to an approved control regimen of irinotecan plus 5-FU/LV in 795 concurrently randomized patients previously untreated for locally advanced or metastatic colorectal cancer. After completion of enrollment, the dose of irinotecan plus 5-FU/LV was decreased due to toxicity. Patients had to be at least 18 years of age, have known locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma not curable by surgery or amenable to radiation therapy with curative intent, histologically proven colorectal adenocarcinoma, measurable or evaluable disease, with an ECOG performance status 0,1, or 2. Patients had to have granulocyte count ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, hemoglobin ≥ 9.0 gm/dL, creatinine ≤ 1.5 x ULN, total bilirubin ≤ 1.5 mg/dL, AST ≤ 5 x ULN, and alkaline phosphatase ≤ 5 x ULN. Patients may have received adjuvant therapy for resected Stage II or III disease without recurrence within 12 months. The patients were stratified for ECOG performance status (0, 1 vs. 2), prior adjuvant chemotherapy (yes vs. no), prior immunotherapy (yes vs. no), and age ( < 65 vs. ≥ 65 years). Although no post study treatment was specified in the protocol, 65 to 72% of patients received additional post study chemotherapy after study treatment discontinuation on all arms. Fifty-eight percent of patients on the ELOXATIN plus 5-FU/LV armreceived an irinotecan-containing regimen and 23% of patients on the irinotecan plus 5-FU/LV armreceived oxaliplatin-containing regimens. Oxaliplatin was not commercially available during the trial.

The following table presents the dosing regimens of the three arms of the study.

Table 19 – Dosing Regimens in Patients Previously Untreated for Advanced Colorectal Cancer Clinical Trial

The following table presents the demographics of the patient population entered into this study.

Table 20 – Patient Demographics in Patients Previously Untreated for Advanced Colorectal Cancer Clinical Trial

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