An exploratory study of body composition as a predictor of dose-limiting toxicity in metastatic pancreatic cancer treated with gemcitabine plus nab-paclitaxel

Youn, Susie; Chen, Angela; Ha, Vincent; Chambers, Carole; Eurich, Dean T.; McCall, Michael; Sawyer, Michael B.

doi:10.1016/j.clnu.2021.06.026

Cited by 14 publications

(9 citation statements)

References 24 publications

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“…Additionally, previously reported retrospective studies have demonstrated that loss of lean body mass and fat mass are common among PDAC patients, independent of body mass index (BMI), associated with poor outcomes 57 , 58 . Notably loss of lean body mass has also been correlated with increased dose limiting toxicities and neuropathy for PDAC patients receiving gemcitabine and nab-paclitaxel 59 .…”

Section: Discussionmentioning

confidence: 99%

Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma

Gong

Thomassian

Kim

et al. 2022

Sci Rep

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In this phase I dose-escalation trial, we assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nanoliposomal Irinotecan (Nal-Iri) and 5-Fluorouracil/Folinic Acid (5-FU/FA). Secondarily, we investigate effects on weight, lean body mass, quality-of-life, the gut microbiome composition, inflammatory biomarkers, progression-free survival, and overall survival. This was a single-arm, open-label adaptive Bayesian dose-escalation study of Bermekimab combined with Nal-Iri and 5FU/FA in patients with advanced or locally advanced PDAC who failed gemcitabine-based chemotherapy. 22 patients enrolled between 2017 and 2019. 3 of 21 patients experienced dose-limiting toxicities attributable to the chemotherapy backbone. 58% (10/17) of patients exhibited weight stability. Physical performance status was preserved among all subjects. Patients reported improvements in quality-of-life metrics via QLQ-PAN26 questioner (−3.6, p = 0.18) and functional well-being (1.78, p = 0.02). Subjects exhibited a decrease in inflammatory cytokines, notably, vascular endothelial growth factor (−0.86, p = 0.017) with Bermekimab. Bermekimab treatment was associated with an increased abundance of gut health-promoting bacterial genera Akkermansia, with 3.82 Log2-fold change from baseline. In sum, Bermekimab is safe to be used in conjunction with Nal-Iri and 5-FU/FA chemotherapy. This benign toxicological profile warrants further Phase I/II investigation of Bermekimab in combinatorial strategies, and the impact of anti-IL-1α antibodies on the gut microbiome.Clinical trials registration: NCT03207724 05/07/2017.

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Section: Discussionmentioning

confidence: 99%

Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma

Gong

Thomassian

Kim

et al. 2022

Sci Rep

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“…Among the 12 studies included, 1 was in the neo-adjuvant setting ( 31 ), 2 in the adjuvant setting ( 30 , 37 ), 3 in the metastatic setting ( 32 , 33 , 36 ); 2 in the unresectable setting ( 26 , 29 ); the other 4 included more than one clinical setting ( 22 , 34 , 35 , 38 ). Eight of the included studies were from Japan ( 22 , 26 , 29 – 32 , 34 , 35 ); 1 from South Korea ( 33 ); 1 from Canada ( 36 ); 1 from Brazil ( 37 ); 1 from Australia ( 38 ); all 12 studies were retrospective ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The Asian studies referred to cut-off values defined for the Asian population, but some used slightly lower cut-off values (26,29,30,34) than others (31)(32)(33). On the other hand, other studies (36)(37)(38) referred either to values elaborated in North America (43) or defined in post-hoc analyses (22). These discrepancies leave space for larger studies to define a proper definition for sarcopenia in PC patients, possibly according to ethnicity, in order to further assess whether an association between sarcopenia and chemorelated toxicity does exist.…”

Section: Discussionmentioning

confidence: 99%

“…The initial search yielded 1137 articles, all in English. According to inclusion and exclusion criteria, 12 full-text articles were included in this systematic review (22,26,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Details about the literature search results are reported in Figure 1.…”

Section: Literature Searchmentioning

confidence: 99%

“…All the articles included evaluated the body composition values at the level of the third lumbar vertebra (L3); the software used was Slice-o-matic (Tomovision) in 5 studies (22,26,(36)(37)(38) and SYN-APSE Vincent in 7 studies (29)(30)(31)(32)(33)(34)(35). As shown in Table 3, body composition parameters evaluated were: SMI (derived from SMA) in 11/12 studies; VAT in 6/12 studies; SAT in 7/12 studies; SMD was evaluated in 3/12 articles; bone mineral density was never evaluated.…”

Section: Technical Aspects and Features Evaluatedmentioning

confidence: 99%

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Body composition as a predictor of chemotherapy-related toxicity in pancreatic cancer patients: A systematic review

Rizzo

Scala

Robayo³

et al. 2022

Front. Oncol.

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ObjectivesThe objective of this systematic review was to assess associations between quantitative body composition measures extracted from imaging examinations and chemotherapy-related toxicity in pancreatic cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across included studies.MethodsThis systematic review was conducted according to the PRISMA statement. A comprehensive literature search of three electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study; population characteristics; technical; body composition features evaluated; CA 19.9 tumor marker levels; chemotherapy drugs administered; toxicities (hematologic, nausea/vomiting, diarrhea, neuropathy, reduction of number of cycles, overall toxicity); association of body composition values with toxicities. The overall quality of the included studies was critically evaluated.ResultsAfter the initial retrieval of 1137 articles, the systematic review included 12 articles (1/12 in the neo-adjuvant setting; 2/12 in the adjuvant setting; 3/12 in the metastatic setting; 2/12 in the unresectable setting; the other 4/12 included more than one clinical setting). The number of patients included ranged between 17 and 251; mean/median age ranged between 63 and 77 years; the percentage of sarcopenic patients ranged between 23 and 76%. The most frequent body composition parameter evaluated was skeletal muscle index (11/12). Chemotherapy regimens included gemcitabine (as monotherapy or in combination with other drugs); FOLFIRINOX and S-1. Among the trials including gemcitabine, 2/9 demonstrated an association with toxicity, whereas 7/9 did not; among those including FOLFIRINOX, one demonstrated associated toxicity whereas the others did not. Altogether, 4/12 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities.ConclusionsThere is a wide variability of results about the association of body composition and chemotherapy-related toxicity in PC patients. Furthermore, cut-off values to define sarcopenia in PC patients are not yet uniformly defined.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337753, identifier CRD42022337753.

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Myelosuppression Caused by Nanoparticle Albumin‐Bound Paclitaxel in the Northern Chinese Population and the Role of Body Composition

Shi

Guo

Jin³

et al. 2023

The Journal of Clinical Pharma

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The aim of this study was to examine the relationship between lean body mass (LBM) and the incidence and severity of neutropenia in patients with malignant tumors from Northern China who have received nanoparticle albumin-bound paclitaxel. Twenty-six patients with pathologically confirmed malignant tumors were prospectively included in this study. These 26 patients were divided into Group A (sarcopenia) and Group B (nonsarcopenia). Group A comprised 50% (13/26) of the patients, while Group B comprised the other 50% (13/26). There was no statistically significant difference between both groups in terms of body surface area (P = .052). The incidence of neutropenia in Group A was 76.9% compared to 61.5% in Group B (P = .0673). The incidence of Grade 3 and severe neutropenia was 76.9% versus 61.5% in Groups A and B, respectively (P = .645). These 26 patients were divided into Groups 1 and 2 based on the administered nab-paclitaxel dose per kilogram of LBM, with both groups receiving a body surface area dose of 260 mg/m 2 . Group 1 received a nab-paclitaxel dose of 14.19 mg/kg of LBM, whereas Group 2 received 11.37 mg/kg of LBM. In Group 1, the incidence of neutropenia was 71.4%, whereas it was 66.7% in Group 2. Grade 3 or higher neutropenia incidence was 28.6% in Group 1 versus 16.7% in Group 2. Patients with sarcopenia in northern China experienced a higher incidence of severe neutropenia after receiving nab-paclitaxel than patients without sarcopenia. Higher drug dose intensity per unit of LBM may be a contributing factor.

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An exploratory study of body composition as a predictor of dose-limiting toxicity in metastatic pancreatic cancer treated with gemcitabine plus nab-paclitaxel

Cited by 14 publications

References 24 publications

Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma

Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma

Body composition as a predictor of chemotherapy-related toxicity in pancreatic cancer patients: A systematic review

Myelosuppression Caused by Nanoparticle Albumin‐Bound Paclitaxel in the Northern Chinese Population and the Role of Body Composition

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