Chemotherapy of large bowel carcinoma—fluorouracil (FU) + hydroxyurea (HU) vs. methyl-CCNU, oncovin, fluorouracil, and streptozotocin (MOF-Strep)

Pf, Engstrom; Jm, MacIntyre; Aj, Schutt; Ho, Douglass

doi:10.1097/00000421-198510000-00004

Cited by 4 publications

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Role of chemotherapy in the treatment of colorectal carcinoma

Kemeny

1987

Seminars in Surgical Oncology

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Large bowel cancer afflicts more patients in the United States than any other malignancy excluding skin cancer. Fifty percent of patients who undergo resection of colorectal carcinoma have positive lymph nodes, and approximately 18% have liver metastases at initial presentation. To improve survival, more effective treatment than surgical resection of the primary must be developed. The most active single agent in the treatment of colorectal carcinoma is 5-fluorouracil (5-FU). To increase the response rate obtained with this agent, work has been done on the modulation of 5-FU by other agents, using drugs that are synergistic with 5-FU and manipulating the method of 5-FU administration. Combination chemotherapy has improved response rates in some situations, though generally it has not been shown to improve survival. Studies using direct hepatic infusion clearly demonstrate an increase in response rates, but again, it is too early to say whether this type of treatment increases survival. Early adjuvant chemotherapy trials used inadequate doses of chemotherapy for short periods of time and demonstrated no added efficacy to surgery alone. Later studies with more aggressive therapy suggested some benefit to treating patients with rectal carcinoma; however, there is still little evidence that adjuvant chemotherapy improves survival in patients with colon carcinoma. To compare and understand the various chemotherapy trials, more stringent reporting of baseline laboratory values, performance status, and estimation of tumor involvement are needed.

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Role of chemotherapy in the treatment of colorectal carcinoma

Kemeny

1987

Seminars in Surgical Oncology

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Leucovorin, 5-fluorouracil, and gemcitabine: A phase I study

et al. 1999

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Gemcitabine is a chemotherapy agent with efficacy in the treatment of lung, pancreas, bladder and breast cancer. It inhibits DNA synthesis by interfering with cytidine triphosphate production and also inhibits the activity of ribonucleotide reductase. Gemcitabine may potentiate fluorouracil's inhibition of thymidylate synthase. This inhibition would be expected to be sequence dependent, occurring only if gemcitabine were administered following fluorouracil (5FU). The combination of leucovorin, 5-FU, and gemcitabine was assessed in this phase I trial. Eligibility requirements included refractory solid tumor malignancy; adequate hematologic, renal and hepatic reserve; no prior therapy with the combination of leucovorin and 5FU, or with gemcitabine; ECOG performance status 0-2, and signed informed consent. Eleven men and nine women were eligible. The median age was 52.5 years and the median performance status was 1. All but three patients had prior chemotherapy. The starting doses were leucovorin 20 mg/m2, 5FU 255 mg/m2 and gemcitabine 600 mg/m2. 5FU and gemcitabine were escalated in tandem to 340 mg/m2 and 800 mg/m2 and thereafter to 425 mg/m2 and 1000 mg/m2, respectively. Gemcitabine administration always followed that of 5FU by 30 minutes. The median number of cycles was 2 (range 1-32). Two patients at the starting dose had disease progression within the first cycle with one death on day 28. One patient with cholangiocarcinoma had a partial response and remained on study for 40 months. There were no other responses. The maximum tolerated dose is leucovorin 20 mg/m2, 5FU 340 mg/m2, and gemcitabine 800 mg/m2. The impact of drug sequence remains undetermined.

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Pharmacological Modulation of Fluoropyrimidines

O’Connor

2005

Combination Cancer Therapy

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Chemotherapy of large bowel carcinoma—fluorouracil (FU) + hydroxyurea (HU) vs. methyl-CCNU, oncovin, fluorouracil, and streptozotocin (MOF-Strep)

Cited by 4 publications

References 0 publications

Role of chemotherapy in the treatment of colorectal carcinoma

Role of chemotherapy in the treatment of colorectal carcinoma

Leucovorin, 5-fluorouracil, and gemcitabine: A phase I study

Pharmacological Modulation of Fluoropyrimidines

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