Abstract
Two cases of squamous cell carcinoma possibly related to exposure to pegylated liposomal doxorubicin are presented.
Keywords: Pegylated Liposomal doxorubicin, Squamous cell carcinoma, Secondary malignancies, Oral tongue carcinoma
Pegylated liposomal doxorubicin (PLD) as single agent is being used in different clinical scenarios, including treatment of recurrent epithelial ovarian cancer, HIV-related Kaposi's sarcoma, and desmoid tumors. Prolonged administration has shown a good safety profile [1–3]. Recently, concerns of a higher risk for oral cavity squamous cell carcinoma in patients with a history of prolonged exposure to PLD was reported [4, 5]. We present two cases of oral tongue cancer in patients who never smoked or drank previously but were exposed to PLD.
The first case is a 35-year-old man with a history of familial adenomatous polyposis/Gardner's syndrome who underwent total colectomy with ileoanal anastomosis for polyposis in 1999. In January, 2004, the patient complained of abdominal distension. An abdominal computed tomography scan showed a 14-cm mesenteric mass. The biopsy was consistent with desmoid tumor. The patient started PLD at a dose of 40 mg/m2 every 4 weeks. Treatment was continued until August, 2006, with continued tumor control. In March 2011, the patient underwent hemiglossectomy with neck dissection. Pathology demonstrated a tumor–node–metastasis (TNM) stage T1N2bM0, poorly differentiated squamous cell carcinoma. In situ hybridization for human papilloma virus (HPV)-16/18 was negative. The patient received concomitant postoperative chemotherapy plus radiation.
The second case is a 47-year-old man with a history of HIV/AIDS and disseminated Kaposi's sarcoma diagnosed in 2002. He started antiretroviral therapy and PLD at a dose of 20 mg/m2 every 4–8 weeks until he attained a complete remission in June of 2005. In March, 2011, he had near-total glossectomy and left-sided selective neck dissection for a stage T3N2bM0, moderately differentiated, squamous cell carcinoma. In situ hybridization for HPV-16/18 was negative. The patient received postoperative radiotherapy.
Carcinomas of the oral cavity are very uncommon in younger patients in the absence of alcohol or tobacco exposure [6, 7]. There is a higher incidence of extracolonic malignancies in patients with Gardner's syndrome but no data linking this entity with squamous cell carcinomas of the oral cavity [8]. Even though there has been an increasing incidence of non-AIDS–defining malignancies in the post–highly active antiretroviral therapy era, the incidence of cancers of the oral cavity in HIV patients is <1% [9]. Treatment of HIV-related Kaposi's sarcoma with PLD has been associated with squamous cell carcinoma of the tongue [2]. It was reported that three of 16 patients with ovarian cancer who were exposed to long-term PLD for a period ≥3 years developed oral cavity malignancies and one patient developed sublingual mucosal high-grade dysplasia [4, 5]. All the lesions were HPV-16/18 negative. Considering that none of our patients were exposed to the risk factors for oral cavity malignancies but were exposed to long-term PLD, our observation, in addition to those cases previously reported [4, 5], supports the hypothesis that long-term exposure to PLD is possibly associated with the development of squamous malignancies of the oral cavity. This long-term toxicity might be explained by the fact that PLD selectively accumulates in the mucosa of the head and neck area [10]. Serial oral cavity examination and a level of suspicion for patients who have received extended courses of PLD appear warranted.
Editor's Note: We publish in this issue a brief series of related papers and letters that examine possible side effects of long-term exposure to pegylated liposomal doxorubicin (PLD). See pages 1534–1540 for a report of the occurrence of the renal thrombotic microangiopathy in ovarian cancer patients exposed to PLD; pages 1541–1546 for a report of squamous cell carcinoma (SCC) of the mouth in non-smoking women with recurrent ovarian cancer; and pages 1596–1599 for two additional Letters to the Editor that relate other cases of SCC of the oral cavity in patients with long-term PLD exposure.
Footnotes
- (C/A)
- Consulting/advisory relationship
- (RF)
- Research funding
- (E)
- Employment
- (H)
- Honoraria received
- (OI)
- Ownership interests
- (IP)
- Intellectual property rights/inventor/patent holder
- (SAB)
- Scientific advisory board
Author Contributions
Conception/Design: Marcelo R. Bonomi, Krzysztof Misiukiewicz, Marshall Posner, Robert G. Maki
Provision of study material or patients: Marcelo R. Bonomi, Krzysztof Misiukiewicz, Marshall Posner, Robert G. Maki
Collection and/or assembly of data: Marcelo R. Bonomi
Data analysis and interpretation: Marcelo R. Bonomi, Marshall Posner, Robert G. Maki
Manuscript writing: Marcelo R. Bonomi, Krzysztof Misiukiewicz, Marshall Posner, Robert G. Maki
Final approval of manuscript: Marcelo R. Bonomi, Krzysztof Misiukiewicz, Marshall Posner, Robert G. Maki
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