CIMETIDINE

Cimetidine blocks histamine and contributes to reducing gastric acid. It has a variety of possible cancer suppressing actions, including reducing metastatic activity levels. Typical of several re-purposed medications, users of cimetidine H2 class anti-histamine show increased progression in some studies, for instance during immunotherapy for lung cancer where H1 class antihistamine supported improved outcomes. Negative effects probably outweigh beneficial ones and cimetidine cannot be recommended other by your oncologist. There are a few apparent promising opportunities that might be interesting below.

An older 2002 pilot study of 64 colorectal cancer patients showed substantially improved 10 year overall survival levels for those with elevated antigens associated with metastatic progression. These bio-markers were shown to be suppressed in patients with cimetidine. A second similar research report from 2000 also showed significant benefits when used during and after surgery for CRC. (Highlights 1 & 2). Addtional 2018 case controlled meta-analysis confirms these improved outcomes and finds benefits are increased with longer usage of a year or more.

Another older study of cimetidine with chemotherapy for advanced stage ovarian cancer showed some improved overall survival results in the 2-3X range, with the largest benefit in high COX-2 patient groups but this needs more evidence. The preliminary promise of cimetidine in some trials has led to its inclusion in new drug development combining it with low-dose cyclophosphamide chemotherapy, diclofenac, and sulfasalazine in oral form, with trials including pancreatic and prostate cancers.

In gastric cancer there are older studies with conflicting results, and in breast cancer effects have so far been lacking. More alarming is the apparent hyperprogression seen in recent trials with immunotherapy in lung cancer. A new study shows less than half the overall survival times with use of H2 class cimetidine (see References below). In stark contrast to the benefits with H1 class. (see Supplements Library).

The present study clearly demonstrated that the beneficial effect of cimetidine given together with 5-FU [chemo] after a curative operation on colorectal cancer patients depended on the degree of expression of the sLx and sLa epitopes on tumour cells. Treatment with cimetidine markedly reduced the frequency of metastasis and significantly increased survival rate in the patients whose cancer cells expressed higher levels of the sLx and the sLa epitopes, but not in the patients whose cancer cells expressed none or lower levels of these epitopes, al...

The authors have previously shown that for patients undergoing resection of colorectal carcinoma, a short perioperative course of cimetidine prevented the development of anergy that affected 84% of control patients at 48 hours.11 They subsequently found, somewhat to their surprise, that this course of cimetidine also produced a trend toward a survival advantage.14 At a median follow-up of 30 months, the calculated 3-year survival was 93% for cimetidine-treated patients and 59% for controls,

Time to recurrence [colorectal cancer] 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 cumula...

Although the number of [ovarian cancer] patients administered cimetidine was relatively small, our findings suggest that adding this drug to systemic chemotherapy for patients with advanced ovarian cancer may prolong their survival…The OS rate of the cimetidine group was significantly higher than that of the control group. The cimetidine group (P<0.05) had a significantly better prognosis than the control group (Fig. 2A). In patients showing high expression of COX-2, the OS rate of the cimetidine group was significantly higher …pla...

TABLE OF REFERENCES

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https://tlcr.amegroups.org/article/view/92203/html	N/A	Moreover, favorable OS was associated with concomitant administration of H1 antihistamines (HR 0.62, 95% CI: 0.39–0.99; P=0.047) and radiotherapy (HR 0.11, 95% CI: 0.02–0.83; P=0.03) (Table 3). Patients who underwent therapy with H2 antihistamines combined with immune checkpoint blockade therapy had a 2.38-fold higher risk of mortality compared to those not receiving concurrent H2 antihistamines.	In the control group, patients who received no antihistamines had a longer OS than those who received only H2 antihistamines after IPTW (25.2 vs. 16.9 months; HR 0.61, 95% CI: 0.37–1.00, P=0.049). These results showed that H1 antihistamine may improve the efficacy of ICI immunotherapy, whereas H2 antihistamine could potentially diminish its effectiveness.
https://www.nature.com/articles/6690457	N/A	Median survival for patients receiving cimetidine was 13 months (95% confidence interval (CI) 9–16 months) and 11 months in the placebo arm (95% CI 9–14 months). There was no significant difference in survival between the two treatment groups (P = 0.42) or between different doses of cimetidine tablets (P = 0.46). Five-year survival of those patients randomized to cimetidine was 21% compared to 18% for those patients randomized to placebo. Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo	We have failed to replicate the findings of Tonneson et al (1988), who reported median survival to be improved from 316 days in placebo recipients to 450 days in those given cimetidine 400 mg twice daily, with a corresponding improvement in relative survival rates from 28% to 45% at 1 year. In a study of 222 gastric cancer patients, median survival appeared markedly greater in those receiving ranitidine 150 mg twice daily (331 days, 95% CI 232–393 days) compared to those receiving placebo treatment (187 days, 95% CI 143–269 days)
https://pmc.ncbi.nlm.nih.gov/articles/PMC2375187/	3.5	Robust beneficial effects of cimetidine were noted: the 10-year survival rate of the cimetidine group was 84.6% whereas that of control group was 49.8% (P<0.0001). According to our previous observations that cimetidine blocked the expression of E-selectin on vascular endothelium and inhibited the adhesion of cancer cells to the endothelium, we have further stratified the patients according to the expression levels of sialyl Lewis antigens X (sLx) and A (sLa). We found that cimetidine treatment was particularly effective in patients whose tumour had higher sLx and sLa antigen levels. For example, the 10-year cumulative survival rate of the cimetidine group with higher CSLEX staining, recognizing sLx, of tumours was 95.5%	The present study clearly demonstrated that the beneficial effect of cimetidine given together with 5-FU after a curative operation on colorectal cancer patients depended on the degree of expression of the sLx and sLa epitopes on tumour cells. Treatment with cimetidine markedly reduced the frequency of metastasis and significantly increased survival rate in the patients whose cancer cells expressed higher levels of the sLx and the sLa epitopes, but not in the patients whose cancer cells expressed none or lower levels of these epitopes, although such a cancer was considered to be less aggressive.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0142(19970701)80:1%3C15::AID-CNCR3%3E3.0.CO;2-E	3	The authors have previously shown that for patients undergoing resection of colorectal carcinoma, a short perioperative course of cimetidine prevented the development of anergy that affected 84% of control patients at 48 hours.11 They subsequently found, somewhat to their surprise, that this course of cimetidine also produced a trend toward a survival advantage.14 At a median follow-up of 30 months, the calculated 3-year survival was 93% for cimetidine-treated patients and 59% for controls,	Therefore the authors examined more closely the immunologic effects within the local tumor environment to find a possible explanation for the production of a long term survival advantage. The authors had already reported that perioperative lymphocyte function was preserved in these colon carcinoma patients by cimetidine.11 An initial review of the routine pathologic reports found that patients receiving cimetidine did in fact demonstrate a higher level of immunoreactivity, with a higher incidence of tumor-infiltrating lymphocytes (TIL). The authors report in the current study that cimetidine significantly increased both the incidence of lymphoid aggregates in association with the carcinoma
https://journals.lww.com/americantherapeutics/abstract/2018/08000/the_effect_of_perioperative_cimetidine.2.aspx	3	. 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).	Prolonged duration of cimetidine may be superior to shorter courses in prolonging recurrence of CRC and thus survival...here was a significant positive relationship between the total cumulative cimetidine dose and survival duration (correlation coefficient = 0.92)
https://www.google.com/url?sa=t&source=web&rct=j&opi=89978449&url=https://www.spandidos-publications.com/10.3892/mmr.1.1.119/	3	Although the number of patients administered cimetidine was relatively small, our findings suggest that adding this drug to systemic chemotherapy for patients with advanced ovarian cancer may prolong their survival...The OS rate of the cimetidine group was significantly higher than that of the control group. The cimetidine group (P<0.05) had a significantly better prognosis than the control group (Fig. 2A). In patients showing high expression of COX-2, the OS rate of the cimetidine group was significantly higher than that of the control group (Fig. 2B, P<0.05). Discussion In the present study, platinum-based chemotherapy combined with cimetidine significantly improved the survival as well as the recurrence rate of patients with advanced stage (FIGO stage III/IV) serous ovarian cancer. These results suggest that cimetidine contributes to an improved prognosis for such patients	In the present study, platinum-based chemotherapy combined with cimetidine significantly improved the survival as well as the recurrence rate of patients with advanced stage (FIGO stage III/IV) serous ovarian cancer. These results suggest that cimetidine contributes to an improved prognosis for such patients. In patients with colorectal or ovarian carcinomas, overex- pression of COX-2 is thought to be associated with resistance to chemotherapy

CIMETIDINE

TABLE OF REFERENCES

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