No abstract

Oncologic emergencies have been extensively described and clearly defined. In oncology daily practice, cancer patients seek non-scheduled medical care in situations they perceive as a medical emergency, but which may not be a true emergency. The aim of the study was to identify the main symptoms leading to a non-scheduled consultation (NSC) and their relationship to the type of cancer, and to evaluate whether the diagnosis at discharge of patients admitted as result of a NSC correlates with a true oncologic emergency. This was a prospective observational study. Between July 2002 and April 2003, 365 NSCs were recorded. The most frequent baseline diseases were breast cancer (70), lung cancer (67), gastrointestinal cancer (52), lymphoma (42) and ovarian cancer (22). The most common symptoms for consultation were: fever (84), pain (81), cutaneous manifestations (26), dyspnea (23), bleeding (16) and abdominal distention (16). Overall, 114 of 365 NSCs (31%) resulted in admission. The most frequent symptoms resulting in admission were fever (42), pain (16), dyspnea (11), vomiting (9), neurologic manifestations (7), abdominal distention (6) and anuria (6). At discharge, only 30 patients (26%) admitted after a NSC were diagnosed with a defined oncologic emergency: febrile neutropenia (13), intestinal occlusion (12), obstructive uropathy (4) and abdominal perforation (1). True emergencies were not the most frequent causes of NSC at our institution.

Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.

Background:PM00104 binds guanines at DNA minor grooves, impacting DNA replication and transcription. A phase I study was undertaken to investigate safety, dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), pharmacokinetics (PKs) and preliminary antitumour activity of PM00104 as a 1- or 3-h infusion three-weekly.Methods:Patients with advanced solid tumours received PM00104 in a dose escalation trial, as guided by toxicity and PK data.Results:A total of 47 patients were treated; 27 patients on the 1-h schedule (0.23–3.6 mg m−2) and 20 patients on the 3-h schedule (1.8–3.5 mg m−2). Dose-limiting toxicities comprised reversible nausea, vomiting, fatigue, elevated transaminases and thrombocytopenia, establishing the 1-h schedule RP2D at 3.0 mg m−2. With the 3-h schedule, DLTs of reversible hypotension and neutropenia established the RP2D at 2.8 mg m−2. Common PM00104-related adverse events at the RP2D comprised grade 1–2 nausea, fatigue and myelosuppression. In both schedules, PKs increased linearly, but doses over the 1-h schedule RP2D resulted in higher than proportional increases in exposure. A patient with advanced urothelial carcinoma had RECIST shrinkage by 49%, and three patients had RECIST stable disease ⩾6 months.Conclusion:PM00104 is well tolerated, with preliminary evidence of antitumour activity observed. The 1-h 3-weekly schedule is being assessed in phase II clinical trials.

PM00104 (Zalypsis®) is a new synthetic alkaloid with potent cytotoxic activity against tumor cell lines. This phase I clinical trial determined the maximal tolerated dose (MTD) and recommended dose (RD) for phase II trials of PM00104 administered as a 1-hour intravenous (i.v.) infusion weekly for three consecutive weeks resting every fourth week (d1,8,15 q4wk). Forty-nine patients with advanced solid malignancies received PM00104 following a toxicity-guided, accelerated, dose-escalation design. Doses evaluated ranged from 0.07 to 3.0 mg/m(2). Dose-limiting toxicities (DLTs) appeared at the highest doses tested and comprised grade 3 diarrhea and grade 4 lipase increase at 2.0 mg/m(2); grade 1 thrombocytopenia and grade 2 neutropenia with two infusion omissions, grade 3 fatigue and grade 4 febrile neutropenia at 2.5 mg/m(2); and grade 3/4 fatigue, grade 4 neutropenia lasting >5 days and grade 4 thrombocytopenia at 3.0 mg/m(2). RD was established at 2.0 mg/m(2). PM00104-related adverse events at the RD were mostly grade 1/2, with fatigue, nausea and vomiting as the most common. Transient and manageable myelosuppression and transaminase increases were also reported. Main pharmacokinetic parameters increased linearly with dose. Disease stabilization lasting ≥ 3 months was found in 4 patients with cervical carcinoma, colorectal adenocarcinoma, lachrymal adenoid carcinoma, and bladder carcinoma (n=1 each). In conclusion, PM00104 2.0 mg/m(2) 1-hour, d1,8,15 q4wk showed a positive risk-benefit ratio, which has supported its further evaluation in three ongoing phase II clinical trials.