Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer? PLD (pegylated liposomal doxorubicin)

Squamous Cell Carcinoma of the Oral Cavity in Non smokingWomen: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

Abstract
Purpose.
To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.

Patients and Methods.
In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed.

Results.
All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m(2) given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD.

Conclusion. 
Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer. 

The finding of oral SCC in patients on long-term PLD
maintenance should alert oncologists to have a high index of
suspicion with any oral complaints that arise, and suggests a
possible need for regular oral examinations in this treatment
population. How long to continue maintenance with PLD after
a CR has been achieved is an unanswered question. The possible
risks to patients receiving maintenance PLD beyond CR
must be weighed against the presumed benefits of delaying
ovarian cancer recurrence on an individual basis.

2011 Cochrane Review: Maintenance chemotherapy for ovarian cancer

EvidenceUpdates- Cochrane Collaboration review: Maintenance chemotherapy for ovarian cancer.

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Cochrane Database Syst Rev. 2010 Sep 8;9:CD007414.

Plain language summary

Maintenance chemotherapy for ovarian cancer
Of all the gynaecological cancers, ovarian cancer has the highest death rate and epithelial ovarian cancer accounts for about 90% of all cases. Surgery and six courses of platinum-based chemotherapy is the standard treatment and 75% of the women may not have any evidence of disease at the end of this treatment. However, 75% of the women who respond to initial treatment will relapse within 18 to 28 months and only 20% to 40% of all women will survive beyond five years.

Some doctors suggest giving maintenance chemotherapy for epithelial ovarian cancer. Maintenance chemotherapy refers to the chemotherapy given to women who have achieved remission after initial surgery and induction chemotherapy.The aim of maintenance chemotherapy is to prolong the duration of remission and improve the overall length of survival. Some studies indicate that maintenance chemotherapy can improve the time without cancer progression, while others do not show any effect. The aim of this review was to establish whether using maintenance chemotherapy is better than observation alone for women with epithelial ovarian cancer. We identified six trials which used different types of chemotherapy (e.g. platinum agents, doxorubicin or topotecan) but there was not sufficient evidence to prove any of the drugs were better than observation alone.

An important consideration for women with advanced disease is the balance between the benefit of treatment and the harms or adverse effects that these treatments may cause. There were insufficient data to comment on the overall impact of the maintenance chemotherapy on clinical benefit from the women's perspective.

Abstract

BACKGROUND: Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer.