A PHASE-I PILOT-STUDY OF PELVIC RADIATION AND ALPHA-2A INTERFERON IN PATIENTS WITH LOCALLY ADVANCED OR RECURRENT RECTAL-CANCER

Purpose: The purpose of this pilot study was to determine the maximum tolerated dose of alpha-2a interferon given by subcutaneous injection and combined with high dose pelvic radiation for locally advanced or r ecurrent rectal cancer. Methods and Materials: In this Phase I pilot s tudy, patients with locally advanced, unresectable, or recurrent recta l cancer with or without distant metastases received external beam pel vic radiotherapy over 5 to 6 weeks combined with escalating doses of a lpha-2a interferon, Interferon was escalated in increments of 3 millio n units for each patient cohort, starting at 3 million units subcutane ously 3 days weekly during pelvic radiation, Radiotherapy consisted of 44 Gy (2 Gy fractions) to the pelvis followed by a boost of 6 Gy or 1 6 Gy to gross pelvic tumor, depending on the presence or absence of sm all bowel in the boost field, respectively, Between 1991 and 1993, 10 patients were treated on this study, five with locally advanced and fi ve with locally recurrent rectal cancer. Results: At 6 million units o f interferon, Grade 3 (WHO criteria) toxicities were as follows: diarr hea (one), leukopenia (one), and neutropenia (one), One patient died o f a massive GI bleed at this dose level, Death was not felt to be trea tment related, The maximum tolerated dose of interferon was 3 million units three times weekly with radiation, Three patients had unusual co mplications at 4, 6, and 6 months possibly related to treatment, The f irst had a right distal ureteric stricture with a right urinoma, The s econd had a sudden left foot drop that has remained stable, The third had sudden onset of bilateral lower extremity paraplegia with spontane ous resolution. Conclusions: The maximally tolerated dose of interfero n alpha-2a given three times weekly during pelvic radiation was 3 mill ion units based on acute side effects, Nevertheless, even at this dose level there were three unusual subacute complications possibly relate d to treatment, Caution is advised when combining interferon alpha-2a with high dose pelvic radiation, especially in patients with predispos ing conditions (such as diabetes) for radiotherapy complications. (C) 1997 Elsevier Science Inc.