Author of

• 12592

  +

  P3.10 - Poster Session 3 - Chemotherapy (ID 210)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12645

    +

    P3.10-053 - Phase II study of a novel taxane (Cabazitaxel-XRP 6258) in previously treated advanced non-small cell lung cancer (NSCLC) patients: toxicity report (ID 3362)

    09:30 - 09:30  |  Author(s): R. Bordoni
    • Abstract

    Background
    Cabazitaxel-XRP6258 is a novel semisynthetic taxane derived from the European yew. In vitro, it has similar microtubules stabilization properties to docetaxel, even against resistant cell lines, due to its lower affinity for P-glycoprotein. Additionally, preclinical models indicated that cabazitaxel was able to cross the blood brain barrier. In addition to prostate cancer, data available from completed phase I, II and III trials showed activity in lung cancer. Based on these data we designed and conducted a phase II trial of Cabazitaxel in the second line treatment of NSCLC.

    Methods
    In this open-label, pilot Phase II trial, subjects with stage IV NSCLC [7[th] Edition of the TNM staging classification, 2009], who have failed first line chemotherapy (platinum doublet or non-platinum doublets, including previous taxane exposure) were randomly treated with either treatment Schedule A (20 mg/m2 every 3 weeks as a 1 hour IV infusion, f/b 25 mg/m2, if no DLTs) or B (8.4 mg/m2 as a 1 hour IV infusion on days 1, 8, 15, and 22 of a 5 week cycle, f/b 10mg/m2, if no DLTs). The primary endpoint was to assess the objective response rate (ORR) of Cabazitaxel-XRP6258. Secondary Objectives were to assess the time to progression (TTP), progression free survival (PFS), overall survival (OS) and safety.

    Results
    Overall the treatment was well tolerated. Among the so far 22 patients enrolled onto the trial, the most commonly found side effects to cabazitaxel were fatigue (18%), anemia (9%), hematuria (8%), neuropathy (6.5%), neutropenia (6%), nausea (6%), and dyspnea (6%), reported as a percentage of the total 141 censored events, compared with the previously most commonly described side effects to cabazitaxel of neutropenia, leukopenia, anemia, diarrhea, fatigue, and asthenia. Most side effects (76%) were grade 1/2 while 23% were grade 3/4; only one patient (4.5%) experienced grade 5 toxicity and succumb to sepsis. The most common adverse effects leading to treatment discontinuation were hematuria and sepsis. Often reported toxicities (over 10%) not found in this cohort includes diarrhea, vomiting, constipation, alopecia, arthralgia and mucosal inflammation. Inversely, the report of hematuria in almost one third of the patients (73% grade 1/2 and 27% grade 3/4) was significant, even more because contrary to the experience with prostate cancer (17% incidence) our population of patients lack the presence of blood in urine at baseline.

    Conclusion
    This Phase II study of cabazitaxel in second line advanced NSCLC showed good tolerance to the drug when administered in two different schedules. The observed side effects are in general consistent with prior reports but hematuria, developed upon exposure to the drug in almost one third of patients. We speculate that cabazitaxel may induce hematuria in cancer patients by direct injury of the urothelial mucosa.