Gemcitabine Plus Cisplatin and Intensity-Modulated Radiation Therapy Improved Response Rate Among Patients With Unresectable Vulvar Squamous Cell Carcinoma

According to results from the phase 2 NRG Oncology/GOG Study 279, gemcitabine plus cisplatin concurrently administered with intensity-modulated radiation therapy (RT) improved complete pathologic complete response (pCR) among patients with locally advanced, unresectable vulvar squamous cell carcinoma. 

“Although gemcitabine has not been used to treat vulvar cancer to date, its chemical and biologic properties, short infusion and same-day administration, made it an attractive agent to combine with cisplatin,” stated Neil S. Horowitz, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. 

In this open-label, single-cohort trial, 52 patients with locally advanced, previously untreated primary vulvar squamous cell carcinoma not amenable to standard radical vulvectomy received 64 Gy of intensity-modulated RT to the vulva plus 50 to 64 Gy of intensity-modulated RT to the groin/low pelvis. Concurrently, patients received 50 mg/m² of gemcitabine plus 40 mg/m² of cisplatin administered once weekly. The primary end point was pCR. Secondary end points included clinical complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events. 

At a median follow-up of 51 months, 73% of patients achieved pCR and 71% of patients achieved clinical CR. Median PFS and OS were not reached, however 12-month PFS was 74% and 24-month OS was 70%. Grade ≥3 adverse events occurred in 44 patients and the most common events included hematologic events, hypomagnesemia, and radiation dermatitis. The trial regimen was completed as prescribed by 42 patients while 6 patients discontinued treatment due to unacceptable toxicity. One patient experienced sudden death which was considered unlikely to be related to the treatment regimen. 

“Compared with historic results, the addition of gemcitabine to cisplatin once per week given concurrently with [intensity-modulated RT] significantly improved the [pCR],” concluded Dr Horowitz et al. “Although toxicities were tolerable, it is unclear if the improved outcome resulted from adding gemcitabine or radiation intensification with [intensity-modulated RT].” 

“A randomized trial would be needed to confirm benefits for the addition of gemcitabine, but this could be considered in patients of good performance status,” added Journal of Clinical Oncology associate editor, Gini Fleming, MD, University of Chicago Medicine, Chicago, Illinois. 

Source: 

Horowitz NS, Deng W, Peterson I, et al. Phase II trial of cisplatin, gemcitabine, and intensity-modulated radiation therapy for locally advanced vulvar squamous cell carcinoma: NRG oncology/GOG study 279. J Clin Oncol. Published online: April 4, 2024. doi: 10.1200/JCO.23.02235