1. Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01)
- Author
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Bok Ai Choo, Nesaretnam Barr Kumarakulasinghe, Johann I. Tang, Valerie Heong, Mellisa Low, Diana Lim, Pearl Tong, Vicky Koh, Yi Wan Lim, Michelle Tseng, Siew Eng Lim, Jeffrey Low, Natalie Ngoi, David S.P. Tan, A. Ilancheran, Yee Liang Thian, Yiat Horng Leong, and Joseph S. Ng
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Neutropenia ,Maximum Tolerated Dose ,Paclitaxel ,Anemia ,medicine.medical_treatment ,Platinum Compounds ,Gastroenterology ,Drug Administration Schedule ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Abdomen ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Patient Reported Outcome Measures ,Adverse effect ,Aged ,Ovarian Neoplasms ,Radiation ,business.industry ,Weekly paclitaxel ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Progression-Free Survival ,Radiation therapy ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Toxicity ,Disease Progression ,Female ,Dose Fractionation, Radiation ,Ovarian cancer ,business - Abstract
Purpose Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC). Methods and Materials Patients were enrolled at de-escalating dose levels of wP (part A), starting at 80 mg/m2, concurrent with fixed-dose LDFWART delivered in 60 cGy fractions twice-daily, 2 days per week, for 6 continuous weeks. After completing the 6-week course of wP + LDFWART, patients received wP until disease progression. Dose-limiting toxicity was evaluated during the first 3 weeks of wP + LDFWART. At wP (80 mg/m2) + LDFWART, no dose-limiting toxicities were observed; this was the established maximum tolerated dose. The trial was expanded (part B) with 7 additional patients with platinum-resistant, high-grade serous ovarian cancer to confirm toxicity and activity. Results A total of 10 heavily pretreated patients were recruited (3 patients to part A, 7 patients to part B). They had received a median of 5 prior lines of therapy, and 70% of patients had received prior wP; 60% of patients completed 6 weeks of wP + LDFWART. Common related grade ≥3 adverse events were neutropenia (60%) and anemia (30%). Median progression-free survival was 3.2 months, and overall survival was 13.5 months. Of patients evaluable for response, 33% (3 of 9) achieved confirmed biochemical response (CA125 decrease >50% from baseline), 11% (1) achieved a partial response, and 5 patients had stable disease, giving a disease control rate of 66.7% (6 of 9). Four patients had durable disease control of ≥12 weeks, completing 12 to 21 weeks of wP. Conclusions The recommended phase 2 dose of wP + LDFWART for 6 weeks is 80 mg/m2. Encouraging efficacy in heavily pretreated PROC patients was observed, suggesting that further development of this therapeutic strategy in PROC should be considered.
- Published
- 2020