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Recurrent Priapism Related to Oxaliplatin Infusion

Department of Gastrointestinal and Genitourinary Oncology, Centre Oscar Lambret, Lille, Catholic University, Lille, France

Audrey Mailliez

Department of Gastrointestinal and Genitourinary Oncology, Centre Oscar Lambret, Lille, France

Jean-Marc Rigot

Andrology Unit, University Hospital, Lille, France

Laurence Gamelin

Antipoison Center, University Hospital, Angers, France

Marie Vanhuyse

Department of Gastrointestinal and Genitourinary Oncology, Centre Oscar Lambret, Lille, Catholic University, Lille, France

Erick Gamelin

Department of Medical Oncology, Centre Paul Papin, Angers, France

To the Editor:

Oxaliplatin combined with fluorouracil (FU) and folinic acid (FA) is accepted worldwide as standard treatment in either the adjuvant or the advanced settings of colorectal cancer. Typically triggered or enhanced by cold exposure, the acute oxaliplatin-induced neurotoxicity occurs during or shortly after oxaliplatin infusion. It is short-lasting and patients recover between cycles. It includes not only specific sensory symptoms such as striking dysesthesia and paresthesia of the hands, feet, and perioral and pharyngolaryngeal region, but also neuromuscular manifestations that mimic neuromyotonia including trismus, muscle cramps, and inability to release grip.^1,2 Calcium (Ca) and Magnesium (Mg) infusions have been advocated by Gamelin et al³ to prevent the oxaliplatin neurotoxicity.

We describe the clinical course of a patient who experienced a reversible longstanding penile erection following the administration of oxaliplatin. This 68-year-old patient underwent first-line chemotherapy for metastatic colon cancer. First-line chemotherapy with irinotecan, FU, FA, and bevacizumab, plus setrons and steroids as antiemetics, was well tolerated but failed to succeed. Then, an oxaliplatin, FU, and FA combination was delivered every 2 weeks with the same antiemetics. After the first cycle and thereafter, the patient presented the expected acute sensory neuropathy related to oxaliplatin exposure. After six cycles, the patient was assessed by a male doctor. At that time, the patient mentioned that he experienced a painless penile erection that lasted from the evening of day 1 of each chemotherapy cycle to the next morning. At cycle 7, the oxaliplatin infusion was replaced by saline fluids. The patient was not aware of the substitution. As expected, he did not present any acute sensory neuropathy or longstanding penile erection. At cycle 8, oxaliplatin was reintroduced and again the patient demonstrated peripheral paresthesia, trismus, and longstanding penile erection. These symptoms did not recur at cycle 12 after the patient had been treated with intravenous Ca and Mg before and after oxaliplatin infusion.

To our knowledge, this is the first case of priapism apparently related to oxaliplatin. Priapism consists of a penile erection that persists or is not related to sexual stimulation.⁴ Different priapism variants have been described, and a few of them have been related to pharmacologic intakes such as antihypertensive, antipsychotic, antidepressant, or erectogenic drugs.⁴ The recurrent prolonged erection experienced by this patient is considered to be oxaliplatin-induced because of (1) the temporal relationship (it occurred within few hours after oxaliplatin-based chemotherapy), (2) the recurrence with rechallenge (it recurred at each oxaliplatin administration), (3) its absence after first-line FU-based chemotherapy and treatments like steroids and setrons, (4) its absence when oxaliplatin infusion was replaced by saline fluids, and (5) its disappearance when Ca/Mg salts were administered. Using the Naranjo probability scale,⁵ a reliable method for estimating the probability of adverse drug reactions, we determined that oxaliplatin is a highly probable causative agent of priapism in this patient. Patients and clinicians should be aware of this extremely rare or underestimated adverse effect related to oxaliplatin infusion.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultrant or Advisory Role: Antoine Adenis, Novartis (C) Stock Ownership: None Honoraria: Antoine Adenis, Amgen (C), Novartis (C) Research Funding: None Expert Testimony: None Other Remuneration: Antoine Adenis, Sanofi-aventis (C), Pfizer (C), Novartis (C)

REFERENCES

1. Gamelin E, Gamelin L, Bossi L, et al: Clinical aspects and molecular basis of oxaliplatin neurotoxicity: Current management and development of preventive measures. Semin Oncol 29:21-33, 2002[Medline]

2. Wilson H, Lehky T, Thomas RR, et al: Acute oxaliplatin-induced peripheral nerve hyperexcitability. J Clin Oncol 20:1767-1774, 2002[Abstract/Free Full Text]

3. Gamelin L, Boisdron-Celle M, Delva R, et al: Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: A retrospective study of 161 patients receiving oxaliplatin combined with 5-fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res 10:4055-4061, 2004[CrossRef][Medline]

4. Montague DK, Jarow J, Broderick GA, et al: American Urological Association guidelines on the management of priapism. J Urol 170:1318-1324, 2003[CrossRef][Medline]

5. Busto U, Naranjo CA, Sellers EM: Comparison of two recently published algorithms for assessing the probability of adverse drug reactions. Br J Clin Pharmacol 13:223-227, 1982[Medline]

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