CORRESPONDENCE

Hiccups as an Adverse Reaction to Cancer Chemotherapy

Yuichi Takiguchi, Reiko Watanabe, Keiichi Nagao, Takayuki Kuriyama

Affiliations of authors: Y. Takiguchi, R. Watanabe, T. Kuriyama (Department of Respirology [B2], Graduate School of Medicine), K. Nagao (Health Sciences Center), Chiba University, Chiba, Japan.

Correspondence to: Yuichi Takiguchi, M.D., Ph.D., Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1–8-1, Inohana, Chuo-ku, Chiba, Japan 260–8670 (e-mail: yuichi{at}med.m.chiba-u.ac.jp).

Although most research reports on cancer chemotherapy have shown no data on the occurrence of hiccups as an adverse reaction, several reports (13) have disclosed a high incidence of hiccups, i.e., in more than 30% of treated patients during chemotherapy. Because most cancer chemotherapy regimens consist of multiple drugs, including cytotoxic agents, 5-hydroxytryptamine3 (5-HT3) receptor antagonists, and corticosteroids, identifying the causative drug is very difficult. Of those drugs, dexamethasone, which is used for the prophylaxis of delayed emesis, has already been shown to cause hiccups (4), although other drugs, including chemotherapeutic agents, cannot be ruled out.

To determine the frequency of hiccups associated with the use of specific chemotherapeutic agents, we have reviewed database information from the corresponding pharmaceutical companies in Japan concerning chemotherapy-induced hiccups. The databases contained data from clinical studies that were used for marketing approval and post-marketing surveillance and from post-marketing clinical studies of each agent used in Japan. The results are summarized in Table 1Go by agent and patient sex. This investigation has at least two shortcomings: information on drug combinations was lacking and some patients treated by combination chemotherapy may have been counted more than once. Be that as it may, the results showed that hiccups occurred in 0.39% of chemotherapy patients on average (range = 0.08% to 6.03%). The most remarkable point, however, is that the total incidence was considerably higher in males (157 of 22 503) than in females (5 of 18 712) (P<.0001, chi-square test). The observation that hiccups are more prevalent in males than in females is not new, according to previous reviews of the literature (4,5). Although most articles in the literature reported on small numbers of patients, those studies found that persistent and intractable hiccups related to epidemic encephalitis, brainstem infarction, and surgery affected predominantly males, whereas the occurrence of hiccups of short duration during the induction and maintenance of anesthesia was an exception to this observation. We do not know the reason for this. We also do not know the frequency with which hiccups occur in either sex, independent of cancer chemotherapy. The information presented here may cast some insight into the mechanisms of hiccups. In any event, the data suggest the importance of evaluating adverse reactions to drugs according to patients' sex.


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Table 1. Incidence of hiccups in patients treated with cancer chemotherapeutic agents*
 

REFERENCES

1 Kris MG, Gralla RJ, Tyson LB, Clark RA, Cirrincione C, Groshen S. Controlling delayed vomiting: double-blind, randomized trial comparing placebo, dexamethasone alone, and metoclopramide plus dexamethasone in patients receiving cisplatin. J Clin Oncol 1989;7:108–14.[Abstract]

2 Sekine I, Nishiwaki Y, Kakinuma R, Kubota K, Hojo F, Matsumoto T, et al. A randomized cross-over trial of granisetron and dexamethasone versus granisetron alone: the role of dexamethasone on day 1 in the control of cisplatin-induced delayed emesis. Jpn J Clin Oncol 1996;26:164–8.[Abstract]

3 Pizzo BA, Pisters KM, Miller VA, Grant SC, Baltzer L, Hinckley L, et al. Oral cisapride for the control of delayed vomiting following high-dose cisplatin. Support Care Cancer 1999;7:44–6.[Medline]

4 Ross J, Eledrisi M, Casner P. Persistent hiccups induced by dexamethasone. West J Med 1999;170:51–2.[Medline]

5 Fisher CM. Protracted hiccup—a male malady. Trans Am Neurol Assoc 1967;92:231–3.[Medline]


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