Palonosetron Plus Megestrol Acetate Versus Palonosetron Plus Dexamethasone in Preventing Moderately Emetogenic Chemotherapy-induced Nausea and Vomiting: A Randomized, Multicenter, Crossover Trial.

Backgrounds: Evidence shows that megestrol acetate (MA) is a potential antiemetic for preventing chemotherapy-induced nausea and vomiting (CINV). No persuasive clinical trials have been performed to validate the efficacy and safety of MA. Here we designed a randomized controlled trial to assess the efficacy of palonosetron plus MA versus palonosetron plus dexamethasone (DEX) in preventing CINV following moderately emetogenic chemotherapy (MEC) regimens.

Methods: This was a multicenter, randomized, single-blinded, crossover, clinical trial practiced in three medical centers. The eligible patients were recruited to the DEX-MA and MA-DEX groups using a computer-generated random number table. Briefly, the DEX-MA group received palonosetron and DEX for the first chemotherapy cycle and then received palonosetron and MA for the second cycle. The MA-DEX group received the antiemetic treatment in the reverse order. Evaluating patients' efficacy and quality of life (QOL) with these two antiemetic regimens. The primary endpoint was complete response (CR). This trial has been registered with the Chinese Clinical Trial Register (ChiCTR2000037447).

Results: Ninety-two patients were enrolled between June 2020 and July 2023, and 86 were eventually evaluated in the study. Forty-one patients were randomized in the DEX-MA group and forty-five in the MA-DEX group. Of all subjects, 51.1% were male, and 48.9% were female. complete response (CR) rates showed no significant difference in the acute phase (0-24 h) (DEX vs. MA, 81.4% vs. 82.6%, P = 0.843), delayed phase (24-120 h) (DEX vs. MA, 81.4% vs. 82.6%, P = 0.843), or overall phase (DEX vs. MA, 72.1% vs. 73.3%, P = 0.864). The QOL showed significant differences in dyspnea symptoms (P = 0.002) and appetite loss symptoms (P = 0.039). This result implied that MA led to less dyspnea, appetite loss, and a better QOL after chemotherapy.

Conclusions: MA may have equivalent efficacy to DEX in the prevention of moderately emetogenic regimen CINV, and no obvious side events occurred. Compared with DEX, MA can significantly improve QOL, especially in decreasing dyspnea and appetite loss. An extension phase III study is going on to validate this observation.