Acute toxicity of neoadjuvant bolus 5-FU/methotrexate and leucovorin rescue followed by continuous infusion 5-FU plus pre-operative radiation therapy for rectal cancer

We present an analysis of acute toxicity of 3 cycles of neoadjuvant bolus methotrexate (MTX) with leucovorin (LV) rescue plus bolus 5-FU, followed by continuous infusion 5-FU with concurrent pre-operative 5040 cGy, and post-operative bolus 5-FU/LV in patients with rectal cancer. Nine patients (1: unresectable, 6: locally advanced, 2: resectable but bulky disease) with adenocarcinoma of the rectum limited to the pelvis were enrolled. For the neoadjuvant segment, the first 4 patients received 3 successive weeks of chemotherapy followed by a 1 week break (continuous course). Due to toxicity, the remaining 5 patients received an intermittent treatment schedule consisting of 3 weekly cycles with 1 week break between cycles 1 and 2 and cycles 2 and 3 followed by a 1 week break (intermittent course). The complete response rates were clinical: 11%, pathologic: 11%, and total: 22%. The incidence of total Grade 3+ toxicity during the neoadjuvant chemotherapy segment was 56% (5/9), and during the pre-operative combined modality segment was 33% (3/9). Therefore, for the entire pre-operative period (neoadjuvant chemotherapy plus pre-operative combined modality segments) 67% (6/9) patients had grade 3+ toxicity. The incidence of total Grade 3+ toxicity during the post-operative combined modality segment was 50% (3/6). The preliminary data suggest that resectability and complete response rates with this neoadjuvant MTX/5-FU/LV plus pre-operative radiation therapy and continuous infusion 5-FU regimen are similar to our prior experience with conventional bolus 5-FU/LV and radiation therapy. However, the incidence of grade 3+ acute toxicity is higher. Additional experience is needed to determine if this approach offers a significant advantage in local control and survival.