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Bakulesh Khamar Khamar



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-94 - Phase I Trial to Establish Maximum Tolerated Dose Safety and Pharmacokinetic Profile of Oral Paclitaxel (ID 13018)

      16:45 - 18:00  |  Author(s): Bakulesh Khamar Khamar

      • Abstract
      • Slides

      Background

      Paclitaxel has been the mainstay of chemotherapy for the treatment of solid tumors like lung ,ovarian, breast, , esophageal, bladder, and head and neck cancers. It is a novel anti microtubule agent which arrests a cell mitotic phase of the cell cycle. Intravenous Paclitaxel is given as every 3 weeks (high dose) or every one week (low dose; metronomic) for many solid tumors. Therapeutic concentration above 85ng/ml for four hours is adequate for efficacy if given every week and is associated with lower toxicity but more frequent clinic visits. To reduce visits, attempts are made to prepare oral formulation without Cremophor. This phase I study was conducted to evaluate pharmacokinetic parameter of novel oral Paclitaxel. (CTRI/2016/02/006607).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this phase I study three dose levels of Paclitaxel oral liquid (100 mg, 200 mg and 300 mg) were evaluated in patients with advanced solid tumors except gastrointestinal cancer under fasting condition.

      4c3880bb027f159e801041b1021e88e8 Result

      Total 9 patients were enrolled in the study, 3 patients in each dose level, with Male: Female ratio of 1:2. The plasma samples from all the patients were analyzed for Paclitaxel concentration. The mean Cmax with 100 mg was 514.9 ng/ml, increased to 767.9 ng/ml with 200 mg and decreased to 380.9 ng/ml with 300 mg. Similar trend was observed with AUC, 1383.7 ng*h/ml, 2732.5 ng*h/ml and 1023.9 ng*h/ml at 100 mg, 200 mg and 300 mg, respectively. These data revealed that Cmax and AUC having linear PK characteristics from 100 to 200 mg and nonlinear PK characteristics from 200 to 300 mg. With 200mg dose therapeutic concentration above 85ng/ml was maintained for about 4 hours indicating its utility as weekly therapy. There were nineteen adverse events (AE) s reported by 8 patients in the form of Malaise,Anemia, Hyponatremia, Rash, Mouth Ulcer, Pain at wound site, Breathlessness, Swelling lips, Vomiting and Weakness. Out of 19 AEs; 09 were mild (Grade I), 09 were moderate (Grade II) and one was severe (Grade III): none of these were related to the study drug.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Oral Paclitaxel was found to be safe and tolerable up to 300 mg dose without any significant safety issues. Its potential in management of advanced solid tumors needs further evaluation as metronomic therapy.

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