First-cycle Toxicities Research Articles

Body Composition Adjusted Dosing of Gemcitabine-Nab-Paclitaxel in Pancreatic Cancer Does Not Predict Toxicity Compared to Body Surface Area Dosing

Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity from this regimen is associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area, derived from height and weight. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. This study included 52 patients who had received first-line treatment with Gem-Nab-P for PDAC. Demographic and chemotherapy treatment information was gathered from medical records and body composition analysis was performed using single slice computed tomography methods, at spinal level L3. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median skeletal muscle area (SkMA) to those who did not (128.6 cm2 vs. 111.4 cm2, P = 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm2 vs. 14.4 mg/cm2, P = 0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm2 vs. 1.8 mg/cm2, P = 0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm2 vs. 2.9 mg/cm2, P = 0.9) between the patients that experienced first cycle toxicity versus those that did not. This study suggests that a PDAC patient’s SkMA is unlikely to be a useful addition to conventional body surface area in the dosing of first-line Gem-Nab-P, to reduce first-cycle toxicity.

The relationship between dose to skeletal muscle area ratio and gemcitabine nab-paclitaxel toxicity in pancreatic ductal adenocarcinoma.

492 Background: Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity is less than that associated with other combination metastatic regimens (FOLFIRINOX), but it is still associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. Methods: This study involved two sites and included patients who had received Gem-Nab-P between January 2013 and March 2017. A review of medical records was used to identify demographic, disease and first-cycle treatment information. Chemotherapy toxicity was defined as grade 3 or 4 adverse events using the National Cancer Institute Common Toxicity Criteria Adverse Events manual v4.0. Body composition analysis was performed on computed tomography scans at spinal level L3, using SliceOmatic software. SPSS software was used to for all statistical analysis, with a p value of < 0.05 considered significant. Results: We identified 52 patients treated with first-line Gem-Nab-P for PDAC. Median age was 65 years (57-73) and 24 (47%) were male. Median BMI at commencement of Gem-Nab-P was 24.7 kg/m2 (21.3-27.4) and 38 (58%) of the patients were myopenic before starting chemotherapy. Fourteen (27%) patients experienced toxicity during the first cycle of chemotherapy. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median SkMA to those who did not (128.6 cm2 vs. 111.4 cm2, p= 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm2 vs. 14.4 mg/cm2, p=0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm2 vs. 1.8 mg/cm2, p=0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm2 vs. 2.9 mg/cm2, p=0.9) between the patients that experienced first cycle toxicity versus those that did not. Conclusions: This study suggests that a pancreatic cancer patient’s skeletal muscle area is unlikely to be a useful addition to conventional body surface area in the dosing of first line Gem-Nab-P, to reduce first-cycle toxicity.

Phase I/II trial of docetaxel plus oxaliplatin and 5-fluorouracil (D-FOX) in patients with untreated, advanced gastric or gastroesophageal cancer

4612 Background: Docetaxel combined with cisplatin/5-fluouracil resulted in significantly longer time-to-progression and survival but also 30% rate of complicated neutropenia (JCO 2006; 24:4991). To improve the safety profile of docetaxel-based therapy, we studied docetaxel with oxaliplatin/5-fluorouracil (D-FOX) to establish the first-cycle MTD (phase II trial to follow). Methods: Patients with histologic proof of gastric or gastroesophageal adenocarcinoma with untreated stage IV cancer were eligible. ECOG PS of <2, near-normal organ function, and written consent were other eligibility criteria. The initial doses of oxaliplatin (85mg/m2) and 5-fluorouracil (2.2g/m2 as 48-hour infusion), given every 2 weeks, were kept constant. Docetaxel was started at 20mg/m2 (Level 1) every 2 weeks in a typical 3x3 phase I design. Subsequent levels (+5mg/m2 every 4 weeks) were added. Fatigue, incompletely treated nausea, and oxaliplatin/5-flurouracil-related toxicities were excluded to determine the MTD. Results: A total of 36 patients have been treated. Currently, docetaxel dose is 47.5mg/m2 every 2 weeks (Level 11). MTD was not reached at Level 10. Overall, grade 3 or 4 first-cycle toxicities have occurred in <5% of patients and without complicated neutropenia. Fifteen of 34 patients have had a confirmed partial response, 13 had stability, and 6 patients had progression. Conclusions: The MTD of D-FOX has not yet been established but its safety profile (D-FOX with 45mg/m2 of docetaxel every 2 weeks) is excellent and the regimen is quite active against untreated gastric or gastoresophageal cancer. Translation studies and additional clinical data will be presented. Supported in part by sanofi-aventis pharma. [Table: see text]