5-fluorouracil and interferon-alpha-2a in advanced colorectal cancer. Results of two treatment schedules.
BACKGROUND
Potential synergy between 5-fluorouracil (5-FU) and interferon alpha-2a (IFN-alpha-2a) has been demonstrated in the treatment of colorectal carcinoma. Continuous low-dose infusion of 5-FU may have superior response rates to bolus 5-FU in these malignancies. This report presents results of two Phase II trials using these principles in colorectal cancer.


METHODS
Forty-eight patients were entered onto two protocols; 18 were treated with 5-FU by a bolus infusion schedule with concurrent IFN-alpha-2a (Group 1). Thirty patients were treated with continuous low-dose 5-FU and IFN-alpha-2a thrice weekly (Group 2).


RESULTS
The overall response rates were 33% (95% confidence interval [CI], 16-68%) and 33% (95% CI, 17-53%), respectively, for Groups 1 and 2. In Group 2, in 16 previously untreated patients, there was a response rate of 56% (95% CI, 30-80%). The median survival was 11 months and 6 months for Groups 1 and 2, respectively. Toxicity in Group 1 was as expected, except the incidence of central nervous system toxicity was low, with only one patient requiring dose reduction because of cerebellar ataxia. The toxicity in Group 2 was substantial, with four patients being removed from study because of toxicity and all patients treated for more than 2 months requiring dose reductions. The most common (67%) toxicity was mucositis, with 33% of those patients classified as Grade III or IV (Southwest Oncology Group criteria). Other major toxicities were fatigue and hand/foot syndrome.


CONCLUSIONS
The first trial confirms previous response rate data for bolus injection 5-FU and IFN-alpha-2a. The second trial of low-dose continuous infusion 5-FU with IFN-alpha-2a demonstrates similar efficacy with substantially greater toxicity.
John
W J
WJ
Lucille Parker Markey Cancer Center, Lexington, KY 40536-0093.
Neefe
J R
JR
Macdonald
J S
JS
Cantrell
J
J
Smith
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002408:Catheters, Indwelling; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D012074:Remission Induction; D013280:Stomatitis / Q000139:chemically induced / Q000209:etiology; D015996:Survival Rate
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil