Key result
Olaparib 100 mg twice daily combined with radiotherapy exceeded the maximum tolerated dose, causing dose-limiting toxicity in 2 of 3 patients, while 1 of 5 patients had toxicity at 50 mg twice daily.
Why the study?
Radical concurrent chemoradiotherapy for oesophageal cancer causes significant morbidity, making PARP inhibitor olaparib an alternative potential radiosensitiser that may be better tolerated.
What is the maximum tolerated dose of olaparib in combination with radiotherapy for oesophageal cancer patients unsuitable for conventional chemoradiotherapy?
What is the maximum tolerated dose of olaparib in combination with radiotherapy for oesophageal cancer patients unsuitable for conventional chemoradiotherapy?
Olaparib 100 mg twice daily exceeds the maximum tolerated dose when combined with radiotherapy in oesophageal cancer patients, while 50 mg twice daily may be the MTD.
100 mg twice daily olaparib with radiotherapy exceeds MTD; leaves open tolerable dosing for future combination trials.
Background and purpose: Radical concurrent chemoradiotherapy (CRT) for oesophageal cancer is associated with significant morbidity and is unsuitable for some patients. Olaparib, an inhibitor of the DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) has radiosensitising properties and may be better tolerated than chemotherapy. Materials and methods: We performed a phase 1 study of olaparib with radiotherapy (RT) in oesophageal cancer patients unsuitable for conventional CRT to determine its maximum tolerated dose (MTD) in this setting. Results: Eight patients were recruited. One of 5 patients receiving olaparib 50 mg twice daily and two of 3 receiving 100 mg twice daily experienced dose limiting toxicity (DLT). Conclusions: Olaparib 100 mg twice daily exceeded the MTD in combination with RT in these patients. 50 mg twice daily may be the MTD but this cannot be stated with certainty as the study closed before full recruitment.
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Sheikh et al. (2023) studied Oesophageal cancer (n=8). Olaparib and radiotherapy was evaluated on Maximum tolerated dose (MTD) based on dose limiting toxicity (DLT). Olaparib 100 mg twice daily combined with radiotherapy exceeded the maximum tolerated dose, causing dose-limiting toxicity in 2 of 3 patients, while 1 of 5 patients had toxicity at 50 mg twice daily.
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