1388PD - Open-label randomized study of individualized pharmacokinetically (PK)-guided dosing versus body surface area (BSA) dosing of paclitaxel (PTX) in a...

Date 09 September 2017
Event ESMO 2017 Congress
Session Supportive and palliative care
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Pharmacology
Non-Small-Cell Lung Cancer, Metastatic
Palliative Care
Lung and other Thoracic Tumours
Palliative and Supportive Care
Presenter Salvatore Salamone
Citation Annals of Oncology (2017) 28 (suppl_5): v497-v501. 10.1093/annonc/mdx382
Authors S.J. Salamone1, J. Zhang2, H. Qi2, H. Ni2, Y. Li1, J.B. Courtney1, C. Zhou3
  • 1Research And Development, Saladax Biomedical, Inc., 18015 - Bethlehem/US
  • 2Department Of Oncology, Shanghai Pulmonary Hospital, 200030 - Shanghai/CN
  • 3Department Of Oncology, Shanghai Pulmonary Hospital, Tongji University, 200433 - Shanghai/CN

Abstract

Background

Variability of PTX exposure using BSA dosing is well documented and often leads to severe toxicities. While carboplatin is dosed to obtain a specific exposure, paclitaxel is conventionally dosed by BSA, leading to a wide range of exposure. This study compared PTX PK-guided dosing to BSA dosing in a PTX-carboplatin regimen treating stage IIIB/IV NSCLC. This is the final analysis of interim results presented at ASCO 2015 (Poster #375). ClinicalTrials.gov Identifier NCT02058433.

Methods

309 patients with stage IIIB/IV NSCLC were randomized to receive up to 4 cycles of first line 3-weekly carboplatin (AUC 5) and a PTX dose of 175 mg/m2 (Arm A), or a PTX PK-guided dose (Arm B) to achieve a time above a PTX plasma concentration of 0.05µM (Tc>0.05) for 26 to 31 hours. Response was classified according to Response Evaluation Criteria in Solid Tumors Group. PTX concentrations were measured by immunoassay; Tc>0.05 was calculated with PK software. The primary endpoint was reduction of grade 4 hematological toxicities.

Results

There were 164 patients in Arm A and 155 patients in Arm B, with 191 males and 128 females participating. PK-guided dose adjustment resulted in doses that were widely distributed 73 – 175 mg/m2, and statistically lower than in the BSA arm (by 24%, p 

Conclusions

Results of this study are in agreement with a previous report, and present further evidence that PK-guided dosing reduces severe toxicities. This is accomplished by an overall lowering of dose intensity, while still maintaining efficacy. PK-guided dosing personalizes chemotherapy, and may be useful in patient management.

Clinical trial identification

02058433.

Legal entity responsible for the study

Tonji University Affiliated Shanghai Pulmonary Hospital, Tongji University

Funding

None

Disclosure

All authors have declared no conflicts of interest.