title: A phase I pilot study of pelvic radiation and alpha-2A interferon in patients with locally advanced or recurrent rectal cancer.
abstract: OBJECTIVE
  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 recurrent rectal cancer.
  
  
  METHODS
  In this Phase I pilot study, patients with locally advanced, unresectable, or recurrent rectal cancer with or without distant metastases received external beam pelvic radiotherapy over 5 to 6 weeks combined with escalating doses of alpha-2a interferon. Interferon was escalated in increments of 3 million units for each patient cohort, starting at 3 million units subcutaneously 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 16 Gy to gross pelvic tumor, depending on the presence or absence of small bowel in the boost field, respectively. Between 1991 and 1993, 10 patients were treated on this study, five with locally advanced and five with locally recurrent rectal cancer.
  
  
  RESULTS
  At 6 million units of interferon, Grade 3 (WHO criteria) toxicities were as follows: diarrhea (one), leukopenia (one), and neutropenia (one). One patient died of a massive GI bleed at this dose level. Death was not felt to be treatment related. The maximum tolerated dose of interferon was 3 million units three times weekly with radiation. Three patients had unusual complications at 4, 6, and 6 months possibly related to treatment. The first had a right distal ureteric stricture with a right urinoma. The second had a sudden left foot drop that has remained stable. The third had sudden onset of bilateral lower extremity paraplegia with spontaneous resolution.
  
  
  CONCLUSIONS
  The maximally tolerated dose of interferon alpha-2a given three times weekly during pelvic radiation was 3 million units based on acute side effects. Nevertheless, even at this dose level there were three unusual subacute complications possibly related to treatment. Caution is advised when combining interferon alpha-2a with high dose pelvic radiation, especially in patients with predisposing conditions (such as diabetes) for radiotherapy complications.
authors.affiliation: Department of Radiation Oncology, London Regional Cancer Centre, Ontario, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Perera
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: W
authors.initials: W
authors.lastname: Kocha
authors.forename: E
authors.initials: E
authors.lastname: Plewes
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: M
authors.initials: M
authors.lastname: Vincent
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D010865:Pilot Projects; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins