Aims of Combined Modality Therapy in Rectal Cancer (M0)

PURPOSE To determine the relationship between acute gastrointestinal (GI) toxicity during the combined modality segment and the volume of small bowel in the pelvic radiation field in patients who receive either preoperative or postoperative therapy for rectal cancer. PATIENTS AND METHODS The patient population was derived from four consecutive phase I dose-escalation trials. Combined modality therapy included fluorouracil (5-FU), leucovorin ([LV] bolus daily x 5, days 1 and 29), and pelvic radiation. RESULTS Twenty patients who received postoperative therapy had a larger volume of small bowel in the pelvic radiation field as compared with 60 who received preoperative therapy (462 +/- 129 v 212 +/- 44 cm3, P = .002). The most significant relationship between acute GI toxicity and volume of small bowel was seen in 12 patients who were treated on the preoperative sequential low-dose LV trial, all of whom received the maximum-tolerated dose (MTD) of 5-FU. The volume of small bowel in patients who experienced grade 3+ toxicity was 731 +/- 274 cm3, as compared with 145 +/- 58 in those who experienced grade 0 to 2 toxicity (P = .005). Likewise, logistic regression analysis showed that 26 patients who received the MTD of 5-FU had the most significant association between GI toxicity and volume of small bowel (P = .036). CONCLUSION Our data suggest that the volume of small bowel in the pelvic radiation field may be dose-limiting in the delivery of high-dose 5-FU when combined with LV and radiation therapy.

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Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.8.1218 ◽

1992 ◽

Vol 10 (8) ◽

pp. 1218-1224 ◽

Cited By ~ 153

Author(s):

B D Minsky ◽

A M Cohen ◽

N Kemeny ◽

W E Enker ◽

D P Kelsen ◽

...

Keyword(s):

Rectal Cancer ◽

Acute Toxicity ◽

Randomized Trials ◽

Combined Modality Therapy ◽

High Dose ◽

Phase I Trials ◽

Postoperative Therapy ◽

Combined Modality ◽

High Incidence ◽

Grade 3

PURPOSE We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer. PATIENTS AND METHODS Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT. RESULTS Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity. CONCLUSION Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.

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