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The Effect of Perioperative Cimetidine Administration on Time to Colorectal Cancer Recurrence

Ali, Ahmad H. MBBS1,2,*; Hale, Laurie RN, MSN3; Yalamanchili, Bindu MD1; Ahmed, Mashrafi MD1,4; Ahmed, Marwa MD1; Zhou, Rixin MD, PhD1; Wright, Stephen E. MD1,3,5

doi: 10.1097/MJT.0000000000000547
Original Articles
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Background: Studies have reported that the perioperative use of cimetidine, a histamine type 2 receptor antagonist, in addition to chemotherapy in patients with lymph node–positive colorectal cancer (CRC) improves the survival.

Study Question: To determine if time to CRC recurrence could be prolonged with cimetidine.

Study Design: Cimetidine was prescribed to American Joint on Cancer Committee (AJCC) stage III CRC patients perioperatively. Tumor recurrence was defined as the time (in days) between tumor resection and CRC recurrence. Medical charts of patients diagnosed with CRC between 1996 and 2006 were reviewed. Inclusion criteria were patients with (a) AJCC stage III CRC, (b) who had undergone surgical resection of the tumor, and (c) who received chemotherapy (5-fluorouracil).

Measures and Outcomes: AJCC stage III CRC patients who did and did not receive cimetidine as part of the treatment regimen were compared with respect to their clinical outcomes using univariate analysis and Kaplan–Meier modeling.

Results: Between 1996 and 2006, 38 patients met our inclusion criteria. Twenty-six percent (10/38) received perioperative cimetidine (mean daily dose, 750 mg; mean duration, 369 days; mean total cumulative cimetidine dose, 274,070 mg/d) in addition to chemotherapy. Time to recurrence and cancer deaths were prolonged in the chemotherapy plus cimetidine group compared with the group that received chemotherapy alone (mean ± SD: 1078 ± 290 vs. 446 ± 62; P = 0.03). In addition, we found a significant positive relationship between the duration of cimetidine therapy (days) and survival duration (correlation coefficient = 0.94, P = 0.02) and time until cancer recurrence (correlation coefficient = 0.99, P = 0.04). Moreover, there was a significant positive relationship between the total cumulative cimetidine dose and survival duration (correlation coefficient = 0.92, P = 0.03).

Conclusions: Prolonged duration of cimetidine may be superior to shorter courses in prolonging recurrence of CRC and thus survival.

1Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX;

2Division of Gastroenterology and Hepatology, Mayo Clinic Collaborative Research Building, Mayo Clinic, Scottsdale, AZ;

3Department of Internal Medicine, Division of Oncology, Thomas E. Creek VA Medical Center, Amarillo VA Health Care System, Amarillo, TX;

4Cardiovascular Medicine, Baystate Medical Center, Springfield, MA; and

5Harrington Cancer Center, Amarillo, TX.

Address for correspondence: Visiting Scientist, Mayo Clinic Collaborative Research building, 13400 E Shea boulevard, Scottsdale, AZ 85259. E-mail: ali.ahmad@mayo.edu

The authors have no conflicts of interest to declare.

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