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. 2024 Jun 1;42(16):1914-1921. doi: 10.1200/JCO.23.02235. Epub 2024 Apr 4.

Abstract

Purpose: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery.

Methods: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0.

Results: Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment.

Conclusion: Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Trial registration: ClinicalTrials.gov NCT01595061.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / mortality
  • Carcinoma, Squamous Cell* / pathology
  • Carcinoma, Squamous Cell* / radiotherapy
  • Carcinoma, Squamous Cell* / therapy
  • Chemoradiotherapy / methods
  • Cisplatin* / administration & dosage
  • Cisplatin* / therapeutic use
  • Deoxycytidine* / administration & dosage
  • Deoxycytidine* / analogs & derivatives
  • Deoxycytidine* / therapeutic use
  • Female
  • Gemcitabine*
  • Humans
  • Middle Aged
  • Progression-Free Survival
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Radiotherapy, Intensity-Modulated* / methods
  • Vulvar Neoplasms* / drug therapy
  • Vulvar Neoplasms* / mortality
  • Vulvar Neoplasms* / pathology
  • Vulvar Neoplasms* / radiotherapy
  • Vulvar Neoplasms* / therapy

Substances

  • Cisplatin
  • Gemcitabine
  • Deoxycytidine

Associated data

  • ClinicalTrials.gov/NCT01595061