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Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01)
- Source :
- International journal of radiation oncology, biology, physics. 109(3)
- Publication Year :
- 2020
-
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.
- 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
Subjects
Details
- ISSN :
- 1879355X
- Volume :
- 109
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- International journal of radiation oncology, biology, physics
- Accession number :
- edsair.doi.dedup.....426432fa86d2f8ef22f2ee5eb2ce26c9