Sequential biochemical modulation of fluorouracil with folinic acid, N-phosphonacetyl-L-aspartic acid, and interferon alfa-2a in advanced colorectal cancer.
OBJECTIVE
Several agents have been evaluated for their effect as biochemical modulators of fluorouracil (5-FU) in the treatment of metastatic colorectal carcinoma. In this study, we used folinic acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNalpha-2a) in a sequential order to assess the efficacy of this approach in patients with metastatic colorectal carcinoma.


METHODS
Forty-four patients with metastatic colorectal carcinoma were enrolled onto the study. The treatment course consisted of three cycles: (cycle 1) FA 20 mg/m(2) followed by 5-FU 425 mg/m(2) on days 1 to 5; (cycle 2) PALA 250 mg/m(2) on days 29, 36, 43, and 50 and 5-FU 2,600 mg/m(2) as a 24-hour infusion on days 30, 37, 44, and 51; and (cycle 3) IFNalpha-2a 9 million units (MU) three times a week for 5 weeks beginning on day 57, with a continuous infusion of 5-FU 750 mg/m(2) on days 57 to 61, and then weekly bolus of 5-FU 750 mg/m(2)/wk on days 71, 78, and 85. Response was determined after cycle 3.


RESULTS
All patients had a Zubrod performance status >/= 2, measurable disease, and had received no prior chemotherapy for their metastatic disease. A total of 212 cycles were given. Thirty-six patients were assessable for response. No complete responses were seen. Seven patients had a partial response, eight had stable disease, and 15 had progressive disease. The median duration of response was 25 weeks, and the median survival was 53 weeks. Grade 3 and 4 toxic effects included granulocytopenia, stomatitis, diarrhea, rash, nausea, and fatigue.


CONCLUSIONS
This trial provided no evidence that sequential biochemical modulation of 5-FU in patients with metastatic colorectal carcinoma had any therapeutic advantage over conventional treatment regimens of 5-FU plus FA.
Royce
M E
ME
Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
McGarry
W
W
Bready
B
B
Dakhil
S R
SR
Belt
R J
RJ
Goodwin
J W
JW
Gray
R
R
Hoff
P M
PM
Winn
R
R
Pazdur
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D002955:Leucovorin; D005472:Fluorouracil