Irinotecan-induced intestinal mucositis in mice: a histopathological study
ConclusionsThe data obtained in the present study provides new evidence that irinotecan-induced intestinal mucositis highly affects small intestine and colon, further contributing to establish criteria in light of the histopathological changes induced by irinotecan during intestinal mucositis and facilitating inter-study comparisons. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 18, 2021 Category: Cancer & Oncology Source Type: research

Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer
ConclusionIntegrated PK/PD, safety, and efficacy data support 240  mg/m2 as the RP2D for trilaciclib.ClinicalTrials.gov IdentifiersNCT02243150; NCT02499770; NCT02514447. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 17, 2021 Category: Cancer & Oncology Source Type: research

Severe toxicity of capecitabine in a patient with DPD deficiency after a safe FEC-100 experience: why we should test DPD deficiency in all patients before high-dose fluoropyrimidines
We report the case of a 44-year-old patient who experienced severe toxicity while being treated with capecitabine at standard dose for metastatic breast cancer. As the patient had already received 5-FU within the FEC protocol (5-FU 500  mg/m2, epirubicin 100  mg/m2, and cyclophosphamide 500  mg/m2) 10  years ago without experiencing any severe adverse event, no DPD deficiency testing was performed before capecitabine treatment. Nevertheless, she experienced severe diarrhea and grade 2 hand–foot syndrome from the first cycle, forcing her to stop the treatment. Phenotypic and genotypic investiga tion of DPD activity re...
Source: Cancer Chemotherapy and Pharmacology - February 15, 2021 Category: Cancer & Oncology Source Type: research

Phase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer
ConclusionThe combination of ruxolitinib and weekly paclitaxel was well tolerated with evidence of clinical activity. Further analysis of this combination is ongoing (NCT02041429).Trial registrationNCT02041429. Date of registration: January 22, 2014. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 14, 2021 Category: Cancer & Oncology Source Type: research

Carboxylesterase 1 polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine
ConclusionsThe identifiedCES1 polymorphisms might provide guide for the identification of gastroenteric cancer patients who were likely to benefit from capecitabine-based chemotherapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 14, 2021 Category: Cancer & Oncology Source Type: research

Acknowledgement of reviewers 2020
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 10, 2021 Category: Cancer & Oncology Source Type: research

Phase II study of an oxaliplatin-based regimen for relapsed colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (INSPIRE study)
ConclusionsFirst-line chemotherapy with re-introduction of OX more than 6  months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 8, 2021 Category: Cancer & Oncology Source Type: research

Preemptive screening of DPYD as part of clinical practice: high prevalence of a novel exon 4 deletion in the Finnish population
AbstractCapecitabine is a fluoropyrimidine that is widely used as a cancer drug for the treatment of patients with a variety of cancers. Unfortunately, early onset, severe or life-threatening toxicity is observed in 19 –32% of patients treated with capecitabine and 5FU. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of 5FU and a DPD deficiency has been shown to be a major determinant of severe fluoropyrimidine-associated toxicity. DPD is encoded by theDPYD gene and some of the identified variants have been described to cause DPD deficiency. Preemptive screening forDPYD gene alteratio...
Source: Cancer Chemotherapy and Pharmacology - February 5, 2021 Category: Cancer & Oncology Source Type: research

Honokiol antagonizes doxorubicin resistance in human breast cancer via miR-188-5p/FBXW7/c-Myc pathway
ConclusionThese findings suggest that downregulation of miR-188-5p by honokiol enhances doxorubicin sensitivity through FBXW7/c-Myc signaling in human breast cancer. Our study finds an important role of miR-188-5p in the development of doxorubicin resistance in breast cancer, and enriches our understanding of the mechanism of action of honokiol in cancer therapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 5, 2021 Category: Cancer & Oncology Source Type: research

BRAF/MEK inhibitors for BRAF V600E-mutant cancers in non-approved setting: a case series
We report five cases of BRAF V600E (substitution of glutamic acid for valine in codon 600) aberrant refractory metastatic cancers treated with dual BRAF/MEK combination inhibitor therapy leading to an excellent clinical and radiological response and protracted duration of disease control. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 3, 2021 Category: Cancer & Oncology Source Type: research

Evaluating clinical impact of a shortened infusion duration for ramucirumab: a model-based approach
ConclusionShortening the infusion duration of ramucirumab from 60 to 30  min has no impact on ramucirumab exposure. Analysis of trial data found no relationship between an increased risk of immediate IRRs and a faster infusion rate. Such a change in infusion duration is unlikely to affect the clinical efficacy or overall safety profile of ramucirumab. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 2, 2021 Category: Cancer & Oncology Source Type: research

Dynamic changes of CTCs in patients with metastatic HR(+)/HER2( −) breast cancer receiving salvage treatment with everolimus/exemestane
ConclusionsThe combination of E/E resulted in early elimination of proliferating CTCs in mBC patients and this effect was associated with a favorable clinical outcome. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 29, 2021 Category: Cancer & Oncology Source Type: research

Extrapolation of pharmacokinetics and pharmacodynamics of sunitinib in children with gastrointestinal stromal tumors
ConclusionBased on PK, safety, and efficacy trial simulations, a sunitinib starting dose of  ~ 25 mg/m2/day was predicted to provide comparable plasma drug exposures in children with GIST as in adults with GIST treated with 50  mg/day. However, in the absence of a tumor type effect of sunitinib on CL/F in children, the projected equivalent dose for this population would be ~ 20 mg/m2/day. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 28, 2021 Category: Cancer & Oncology Source Type: research

A phase 1 trial of 4-(N-(S-penicillaminylacetyl)amino)-phenylarsonous acid (PENAO) in patients with advanced solid tumours
ConclusionsPENAO was administered by CIVI at dose levels up to 9  mg/m2/day with only one DLT noted. Pharmacokinetic studies invalidated the rationale for continuous dosing and led to discontinuation of the trial without defining a RP2D. Future clinical development of PENAO will use intermittent dosing schedule, alone and in combination with rapamycin. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 26, 2021 Category: Cancer & Oncology Source Type: research

A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies
ConclusionSingle-agent AR-42 is safe and well tolerated. Further studies may consider AR-42 in a larger cohort of patients with NF2 or in combination with other agents in advanced solid tumors.Trial registrationNCT01129193, registered 5/24/2010. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 25, 2021 Category: Cancer & Oncology Source Type: research