plitidepsin and Lung-Neoplasms

To assess clinical benefit of plitidepsin (Aplidine) in patients with advanced medullary thyroid carcinoma (MTC).. We retrospectively reported the outcome of 10 patients with advanced MTC among 215 patients who have entered the phase I program with plitidepsin.. Median number of cycles was 5. Using World Health Organization criteria, 1 among 5 patients with measurable disease displayed a confirmed partial response, whereas 8 patients experienced a stable disease, and 1 patient had a progressive disease, corresponding to a disease control rate of 90%. Two patients treated at the maximum tolerated dose experienced muscular dose-limiting toxicity possibly related to palmitoyl transferase inhibition. One of these 2 patients was able to continue therapy with no dose reduction with the prophylactic addition of l-carnitine, which is used in the treatment of the carnitine palmitoyl transferase deficiency type 2.. Plitidepsin seems to be able to induce clinical benefit in patients with pretreated MTC, and its toxicity has been manageable at the recommended dose.

Topics: Adult; Aged; Antineoplastic Agents; Bone Neoplasms; Carcinoma, Medullary; Depsipeptides; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Male; Marine Toxins; Maximum Tolerated Dose; Middle Aged; Peptides, Cyclic; Survival Rate; Thyroid Neoplasms; Treatment Outcome

To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy.. This was a multicenter, open-label, single-arm, exploratory, phase II clinical trial. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST). The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0.. Twenty pretreated SCLC patients (median age, 60 years) with extensive (n = 13) or limited-stage disease (n = 7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2). Objective tumor responses were not observed and only one of the 17 evaluable patients had SD. With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively. The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase.. This clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC. One patient died due to multi-organ failure. The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Antineoplastic Agents; Bone Neoplasms; Depsipeptides; Female; Humans; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Peptides, Cyclic; Prognosis; Salvage Therapy; Skin Neoplasms; Small Cell Lung Carcinoma; Survival Rate; Treatment Outcome

To evaluate the progression-free rate (PFR) at 3 months (13+/-1 weeks), antitumor response, time-to-event efficacy endpoints, and toxicity profile of plitidepsin administered as a 3-h continuous i.v. infusion at a dose of 5mg/m(2), every 2 weeks, to patients with chemotherapy pretreated advanced non-small cell lung cancer (NSCLC).. This was a multicenter, non-randomized, exploratory, phase II study. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. PFR (primary efficacy endpoint) and objective response rate (secondary efficacy endpoint) were evaluated according to RECIST, while the toxic profile of plitidepsin was assessed using the NCI-CTC, version 2.0.. A total of 21 patients with a median age of 61 years and with locally advanced or metastatic non-resectable NSCLC, who had previously received only one line of chemotherapy in an advanced setting, received a total of 54 cycles of treatment (median of two cycles per patient; range: 1-8). Antitumor activity was seen in 3 (1 PR, 2 SD) out of 17 evaluable patients according to RECIST. One patient was responder for the primary (PFR at 13+/-1 weeks) and secondary efficacy endpoint (stable disease according to RECIST). Other two patients were non-responders for the primary efficacy endpoint, but had stable disease (not confirmed at weeks 13+/-1 due to previous withdrawal due to adverse events). With a median follow-up of 12.3 months, the median time to progression (TTP) and the median overall survival (OS) were 1.2 months and 4.3 months, respectively. The incidence of plitidepsin-related toxicities was low and most of them were mild-to-moderate in severity. The most common side effects were anemia, and asymptomatic and non-cumulative increases of gamma-glutamyltransferase (GGT) and liver transaminase levels.. This study shows that plitidepsin 3-h continuous i.v. infusion (5mg/m(2)) every 2 weeks, was feasible and well tolerated in patients with pretreated NSCLC. The lack of evidence of antitumor activity precludes further studies with this plitidepsin schedule in this tumor setting.

Topics: Adult; Aged; Anemia; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Depsipeptides; Disease Progression; Disease-Free Survival; Female; gamma-Glutamyltransferase; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Peptides, Cyclic; Transaminases; Urochordata