Dose‐limiting toxicities and recommended dose
nausea, pneumonia, DLTs, diarrhea, toxicities, nausea and vomiting, vomiting, PD
PNEUMONIA
Twelve of the 22 patients treated at the escalation stage were evaluable for dose‐limiting toxicities (DLTs).The other10 patients were non‐evaluable for RD. Six of these patients did not receive a complete Cycle 1 (two patients discontinued before ending Cycle 1 due to pneumonia unrelated to treatment, one due to early PD, one due to plitidepsin hypersensitivity reaction, one patient had treatment omission due to treatment‐related grade 1 nausea and vomiting, and one patient due to missed oral DXM dose). Of the other four patients, two received incorrect BTZ or DXM doses at Cycle 1, one received treatment on Days 4 and 11 despite not fulfilling treatment criteria, and one had no laboratory tests done in Cycle 1.No DLTs occurred during dose escalation. Dose escalation beyond DL3 was not allowed by the study protocol; hence, DL3 (plitidepsin 5.0, BTZ 1.3 mg/mAt the RD cohort, 12 of the 24 treated patients were evaluable for DLTs. Two patients (17%) had DLTs during Cycle 1; these DLTs consisted of grade 3 diarrhea, and a combination of grade 3 nausea and grade 3 vomiting refractory to antiemetic therapy, in one patient each.