Correspondence

Chemotherapy for Colorectal Cancer

N Engl J Med 1994; 331:680-681September 8, 1994

Article

To the Editor:

We believe that hepatic atrial infusion, new drugs, and biochemical modulation deserve more attention than they received in Dr. Moertel's review of chemotherapy for colorectal cancer (April 21 issue)1. With respect to hepatic arterial infusion, two large studies with a crossover design demonstrated survival advantages for patients who were crossed over from systemic to hepatic arterial chemotherapy; two studies in which there was no survival advantage associated with hepatic therapy involved only small numbers of patients2. In the study by the National Cancer Institute,2 the median survival was 22 and 12 months for the groups receiving hepatic arterial infusion and systemic therapy, respectively, but the small number of patients (64) may have precluded a statistically significant difference in survival. In the Mayo Clinic study,2 49 percent of the 36 patients receiving hepatic arterial infusion were not adequately treated, which potentially affected the results. In recent studies of hepatic arterial infusion, the median survival is over 27 months and the 2-year survival is 64 percent3.

A new drug, irinotecan (CPT-11, a topoisomerase inhibitor), has a major-response rate of 30 and 25 percent in previously untreated and treated patients, respectively4. Tomudex, a thymidylate synthase inhibitor, has produced responses in 25 to 30 percent of patients. Treatments such as fluorouracil infusions or low-dose N-(phosphonoacetyl)-l-aspartic acid with fluorouracil yield a response rate of 30 percent,5 with a survival rate similar to that associated with fluorouracil plus leucovorin.

Certain key points regarding fluorouracil plus leucovorin and fluorouracil plus levamisole should also be emphasized. A recent meta-analysis of studies involving 1381 patients showed no advantage in survival associated with fluorouracil plus leucovorin,2 and the side effects and cost increased with the addition of leucovorin. Although previous studies of adjuvant therapy have demonstrated that fluorouracil alone is ineffective, these trials were flawed because of suboptimal doses of fluorouracil, erratic absorption of oral fluorouracil, long intervals between cycles of chemotherapy, and an insufficient period of treatment. Levamisole is expensive ($2,600 per year) and increases neurologic and hepatic side effects1. Whether fluorouracil alone could have produced similar results with less cost and toxicity has not been addressed.

Nancy E. Kemeny, M.D.
John A. Conti, M.D.
Joseph R. Bertino, M.D.
Memorial Sloan-Kettering Cancer Center, New York, NY 10021

5 References

1. 1

   Moertel CG. Chemotherapy for colorectal cancer. N Engl J Med 1994;330:1136-1142
   Full Text | Web of Science | Medline

2. 2

   Kemeny N, Selter K. Colorectal carcinoma. In: Calabresi P, Schein P, eds. Medical oncology: basic principles and clinical management of cancer. 2nd ed. New York: McGraw-Hill, 1993:749-82.
   

3. 3

   Kemeny N, Cohen A, Bertino JR, Sigurdson ER, Botet J, Oderman P. Continuous intrahepatic infusion of floxuridine and leucovorin through an implantable pump for the treatment of hepatic metastases from colorectal carcinoma. Cancer 1990;65:2446-2450
   CrossRef | Web of Science | Medline

4. 4

   Shimada Y, Yoshino M, Wakui A, et al. Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. J Clin Oncol 1993;11:909-913
   Web of Science | Medline

5. 5

   Kemeny N, Lokich JJ, Anderson N, Ahlgren JD. Recent advances in the treatment of advanced colorectal cancer. Cancer 1993;71:9-18
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Hidekazu Kuramochi, Kazuhiko Hayashi, Kazumi Uchida, Satoru Miyakura, Daisuke Shimizu, Daniel Vallbohmer, Seongjin Park, Kathleen D. Danenberg, Ken Takasaki, Peter V. Danenberg. (2006) 5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis. International Journal of Cancer 119:3, 522-526
   CrossRef

2. 2

   David Blumberg, Ramesh K. Ramanathan. (2002) Treatment of Colon and Rectal Cancer. Journal of Clinical Gastroenterology 34:1, 15-26
   CrossRef