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

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 492-492
Author(s):  
Rachel Wong ◽  
Julia Freckelton ◽  
Daniel Croagh ◽  
Darcy Quinn Holt ◽  
Adrian Fox ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Ductal Adenocarcinoma ◽  
First Line ◽  
Muscle Area ◽  
Skeletal Muscle Area

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.

Skeletal muscle area correlates with body surface area in healthy adults

2013 ◽  
Vol 44 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Tomoharu Yoshizumi ◽  
Ken Shirabe ◽  
Hidekazu Nakagawara ◽  
Toru Ikegami ◽  
Norifumi Harimoto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Healthy Adults ◽  
Muscle Area ◽  
Skeletal Muscle Area

SBP-101, a polyamine metabolic inhibitor, administered in combination with gemcitabine and nab-paclitaxel, shows signals of efficacy as first-line treatment for subjects with metastatic pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4127-4127
Author(s):  
Nimit Singhal ◽  
Darren Sigal ◽  
Niall C. Tebbutt ◽  
Aram F Hezel ◽  
Adnan Nagrial ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Retinal Toxicity ◽  
Ductal Adenocarcinoma ◽  
Metabolic Inhibitor ◽  
Line Treatment ◽  
Hepatic Toxicity ◽  
First Line ◽  
Phase 1B ◽  
First Line Treatment

4127 Background: SBP-101, a polyamine metabolic inhibitor, inhibited growth in 6 human pancreatic ductal adenocarcinoma (PDA) cell lines and 3 murine xenograft tumor models of human PDA. SBP-101 monotherapy in heavily pre-treated PDA patients (> 2 prior regimens) showed a median survival of 5.9 months at the optimal dose level. Purpose: To assess the PK, safety and efficacy of SBP-101 in combination with gemcitabine (G) and nab-paclitaxel (A) in patients with previously untreated metastatic PDA. Methods: In a modified 3+3 dose escalation scheme, subcutaneous injections of SBP-101 were dosed at 0.2, 0.4 or 0.6 mg/kg days 1-5 of each 28-day cycle. G (1000 mg/m2) and A (125 mg/m2) were administered intravenously on Days 1, 8, and 15 of each cycle. PK was evaluated on day 1 of cycle 1 in cohorts 1-3. Safety was evaluated by clinical and laboratory assessments. Efficacy was assessed by CA19-9 levels, objective response using RECIST criteria, progression-free survival (PFS) and overall survival (OS). A fourth cohort using a modified dosing schedule of 0.4 mg/kg SBP-101 days 1-5 for cycles 1-2 and days 1, 8, and 15 every cycle thereafter was added to mitigate hepatic toxicity, and that dose and schedule were recommended for phase 1b expansion. Interim Results: Fifty patients were enrolled (N=25, phase 1a and N=25, phase 1b) and have received up to 12 treatment cycles. SBP-101 plasma Cmax and AUC0-t increased in a slightly more than dose proportional manner and were unchanged by the addition of G and A. PK parameters of G and A were unaltered by increasing doses of SBP-101. The most common nonserious adverse events related to SBP-101 (>10%) are fatigue (N=15), LFT/transaminase abnormalities (N=15), vision abnormalities (N=6), injection site pain (N=13), dehydration (N=7), diarrhea (N=7) and nausea (N=6). Serious adverse events related to SBP-101 observed in some subjects include hepatic toxicity (N= 6) and retinal toxicity (N=6) both occurring after prolonged treatment and requiring dose reduction or discontinuation. There is no evidence of SBP-101-related bone marrow suppression or peripheral neuropathy. At the recommended dose and schedule (N=30), CA19-9 levels decreased 60-99% in 19 of 29 evaluable patients, with 12/28 evaluable patients achieving partial responses (43%) and 11/28 achieving stable disease at 8 weeks (39%). Nine subjects are ongoing. PFS was confounded by SBP-101 dosing holds implemented to investigate potential toxicity. Median OS has not been reached. Conclusions: Interim results suggest SBP-101 may enhance first-line treatment with G and A in patients with metastatic PDA. Hepatic toxicity can be mitigated with dose reduction or discontinuation. Retinal toxicity that occurred in some subjects is under investigation. Clinical trial information: NCT03412799.

scholarly journals Progressive exercise training improves maximal aerobic capacity in individuals with well-healed burn injuries

2019 ◽  
Vol 317 (4) ◽  
pp. R563-R570 ◽  
Author(s):  
Steven A. Romero ◽  
Gilbert Moralez ◽  
Manall F. Jaffery ◽  
Mu Huang ◽  
Matthew N. Cramer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Surface Area ◽  
Body Surface Area ◽  
Aerobic Capacity ◽  
Body Surface ◽  
Burn Injuries ◽  
Maximal Aerobic Capacity ◽  
Area Burned ◽  
Progressive Exercise

Long-term rehabilitative strategies are important for individuals with well-healed burn injuries. Such information is particularly critical because patients are routinely surviving severe burn injuries given medical advances in the acute care setting. The purpose of this study was to test the hypothesis that a 6-mo community-based exercise training program will increase maximal aerobic capacity (V̇o2max) in subjects with prior burn injuries, with the extent of that increase influenced by the severity of the burn injury (i.e., percent body surface area burned). Maximal aerobic capacity (indirect calorimetry) and skeletal muscle oxidative enzyme activity (biopsy of the vastus lateralis muscle) were measured pre- and postexercise training in noninjured control subjects ( n = 11) and in individuals with well-healed burn injuries ( n = 13, moderate body surface area burned; n = 20, high body surface area burned). Exercise training increased V̇o2max in all groups (control: 15 ± 5%; moderate body surface area: 11 ± 3%; high body surface area: 11 ± 2%; P < 0.05), though the magnitude of this improvement did not differ between groups ( P = 0.7). Exercise training also increased the activity of the skeletal muscle oxidative enzymes citrate synthase ( P < 0.05) and cytochrome c oxidase ( P < 0.05), an effect that did not differ between groups ( P = 0.2). These data suggest that 6 mo of progressive exercise training improves V̇o2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response.

Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 724-724 ◽  
Author(s):  
Hirochika Toyama ◽  
Teiichi Sugiura ◽  
Akira Fukutomi ◽  
Hirofumi Asakura ◽  
Yuriko Takeda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Combination Chemotherapy ◽  
Neoadjuvant Treatment ◽  
The Body ◽  
Ductal Adenocarcinoma ◽  
Clinical Trial Registry ◽  
Chemotherapy Group

724 Background: Although neoadjuvant treatment (NAT) has been widely employed for resectable pancreatic ductal adenocarcinoma (PDAC), it is still unclear what kind of regimen is recommended. The aim of the study is to investigate which chemoradiotherapy (CRT) with S-1 or combination chemotherapy with gemcitabine (GEM) and S-1 is more promising as NAT for resectable PDAC in terms of effectiveness and safety. Methods: Patients with resectable PDAC were enrolled and randomly assigned into either CRT group or chemotherapy group. In the CRT group, a total radiation dose of 50.4 Gy in 28 fractions was administered and S-1, at a dose of 30, 40 or 50 mg according to the body surface area, was orally provided twice a day on the same day of irradiation. In the chemotherapy group, GEM was intravenously administered at a dose of 1000 mg/m2 on day 1 and 8 and S-1 was orally provided at a dose of 30, 40 or 50 mg according to the body surface area twice daily on day 1 to 14 followed by one week reset. Patients in the chemotherapy group received two cycles of this regimen. Surgery was performed between 15 and 56 days after the last day of NAT. The primary endpoint was 2-year progression-free survival (PFS) rate. With 50 patients in each group, the study had 80% power assuming a threshold 2-year PFS rate of 25% and an expected 2-year PFS rate of 40% at 0.05 one-sided alpha. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 and April 2017, 103 patients were enrolled from 11 institutions in Japan. One was excluded because of ineligibility, therefore 51 patients in CRT group and 51 patients in chemotherapy group constituted the intention-to-treat analysis. The 2-year PFS rate was 45% (90% CI, 33-60%) in the CRT group and 55% (43-65%) in the chemotherapy group (p = 0.52). The hazard ratio for chemotherapy to CRT was 0.78 (0.46-1.31). The median survival time was 37.7 (95% CI, 30.3-NE) in the CRT group and NE (29.9-NE) in the chemotherapy group (p = 0.30). There was no treatment-related death in both groups. Conclusions: Combination chemotherapy with GEM and S-1 may be more promising compared with CRT with S-1 as NAT for resectable PDAC. Clinical trial information: UMIN000014894.

scholarly journals Capecitabine (cape) dosing using skeletal muscle index (SMI) compared to body surface area (BSA)

2016 ◽  
Vol 27 ◽  
pp. vi179
Author(s):  
J. Sun ◽  
A. Ilich ◽  
C. Kim ◽  
G. Wong ◽  
S. Ghosh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Skeletal Muscle Index

Modification of Calcium Flux of Twitch Skeletal Muscle in Mice Subjected to 20% Body Surface Area Burn

1992 ◽  
Vol 13 (5) ◽  
pp. 546-555 ◽  
Author(s):  
John F. Tomera ◽  
Kevin D. Friend ◽  
Steven P. Kukulka ◽  
Karen Lilford
Keyword(s):  
Skeletal Muscle ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Calcium Flux

Actual body weight dosing of temozolomide and overall survival in patients with glioblastoma

2020 ◽  
pp. 107815522096861
Author(s):  
Phoebe (Yu Hsuan) Hsu ◽  
Frances Folkman ◽  
Sunita Ghosh ◽  
Paula de Robles ◽  
Catriona Leckie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Body Weight ◽  
Actual Body ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Actual Body Weight ◽  
Pivotal Trial ◽  
First Line ◽  
Cut Point

Background Adult glioblastoma patients receiving standard radiation therapy and concurrent temozolomide chemotherapy have a median survival of 14.6 months. Based on the pivotal trial data by Stupp et al., temozolomide doses were calculated based on body surface area. However, no details regarding the weight used to calculate body surface area was included in the study. As a result, temozolomide doses have been variable across the province. Methods This retrospective chart review was conducted to determine the correlation between dose of first line temozolomide with overall survival. Patients between January 1st, 2009 and December 31st, 2014 who were newly diagnosed, pathology confirmed glioblastoma treated first line with temozolomide within Alberta Health Services were included in the study. Temozolomide doses above and below determined cut points were compared through the Kaplan-Meier method, then assessed using the log-rank test. Results A cut point of 97.8% of actual body weight calculated body surface area dosing was determined for concurrent phase temozolomide. At doses above this cut point, there was a statistically significant (p = 0.0158) increase of 0.3 years in median overall survival. As for toxicity concerns, there was a statistically significant increase in the proportion of temozolomide dose reductions due to toxicity in patients dosed above the cut point. Conclusion Temozolomide doses at full actual body weight calculated body surface area dosing during the concurrent phase is required to achieve a similar median OS as seen in the pivotal trial by Stupp et al.

Efficacy and safety of KN046 plus nab-paclitaxel/gemcitabine as first-line treatment for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4138-4138
Author(s):  
Gang Jin ◽  
Shiwei Guo ◽  
Yanqiao Zhang ◽  
Yue Ma ◽  
Xiaodong Guo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Therapy ◽  
Locally Advanced ◽  
Tumour Response ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

4138 Background: Pancreatic ductal adenocarcinoma（PDAC）is one of the most lethal malignancies worldwide and is characterized by extremely poor prognosis. Nab-paclitaxel plus gemcitabine has been recommended by international guidelines for first-line treatment of advanced PDAC but chemoresistance is difficult to avoid. Combination of immune checkpoint inhibitors (ICIs) and chemotherapy has demonstrated substantial promise for the treatment of several advanced malignancies. A few recent studies have begun to explore the effect of ICIs monotherapy or co in advanced PDAC with few meaningful results. KN046, a novel recombinant humanized bispecific antibody, can simultaneously block PD-1/PD-L1 and CTLA-4 pathways and restore T-cell immune response to tumor. The purpose of this study is to evaluate the efficacy and safety of KN046 plus nab-paclitaxel/gemcitabine as first-line treatment for unresectable locally advanced or metastatic PDAC. Methods: This ongoing phase II trial in China enrolled pts with histologically or cytologically confirmed unresectable locally advanced or metastatic PDAC who have ECOG PS of 0-1 and never received systemic anti-tumor therapy for advanced or metastatic diseases. KN046 (5mpk, Q2W) plus nab-paclitaxel (125mg/m2, D1, 8, 15, Q4W) and gemcitabine (1000mg/m2, D1, 8, 15, Q4W) were administered 4-6 cycles followed by KN046 (5mpk) maintenance therapy every 2 weeks. Tumour response was assessed according to RECIST 1.1 every 8 weeks. The primary endpoint is investigator-assessed ORR. Secondary endpoints are DCR, DOR, TTP, PFS, OS and safety. Results: As of December 15, 2020, 17 pts were enrolled, median (range) age was 56 (36-75) years, 9 pts ECOG 1, and 7 pts had liver metastases. Median KN046 exposure time was 9.5 wks. 9 pts were included in the efficacy analysis and 17 pts in the safety analysis. In best overall response assessment, there were 55.6% PR (5/9) and 33.3% SD (3/9). ORR was 55.6% (95% CI: 21.2̃86.3), and DCR was 88.9% (95% CI: 51.8̃99.7). The overall incidence of KN046 related treatment-emergent adverse events was 64.7%, with 29.4% were grade 3 TRAE. The most common KN046 related treatment-emergent adverse events (≥10%) were alanine aminotransferase increased (n = 5, 29.4%), nausea (n = 3, 17.6%), rash (n = 3, 17.6%), aspartate aminotransferase increased (n = 2, 11.8%), diarrhoea (n = 2, 11.8%), hyperphosphataemia (n = 2, 11.8%), pyrexia (n = 2, 11.8%), vomiting (n = 2, 11.8%). Conclusions: Combining KN046 with nab-paclitaxel and gemcitabine as first-line treatment for unresectable locally advanced or metastatic PDAC patients is safe and feasible, and lays the foundation for subsequent clinical trials. Clinical trial information: NCT04324307.

Sign in / Sign up

Export Citation Format

Share Document