Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background

Sunitinib therapy for patients with imatinib-resistant and/or intolerant gastrointestinal stromal tumors (GISTs) often causes severe adverse events (AEs) that lead to treatment discontinuation.

Methods

We retrospectively reviewed the clinical records of imatinib-resistant and/or intolerant GIST patients who underwent sunitinib therapy in our institutions between 2007 and 2020. Forty-one patients were enrolled and divided into two groups on the basis of the starting dosage: the standard dosage group (50 mg/day, 21 patients) and the reduced dosage group (37.5 mg/day, 20 patients). Tolerability, safety and clinical efficacy of the two groups were compared.

Results

Three patients (14%) in the standard dosage group and another three (15%) in the reduced dosage group (P = 1.000) discontinued sunitinib therapy because of AEs. The incidences of grade 3 or more severe treatment-related AEs were 90 and 75%, respectively (P = 0.238). Two possible treatment-related deaths were noted in the standard dosage group. Clinical efficacy was comparable between the two groups: median time to treatment failure and overall survival were 4.5 months [interquartile range (IQR), 3.6–9.0] and 13.7 months (IQR, 7.5–22.9) in the standard dosage group and 4.6 months (IQR, 2.7–17.0) and 13.4 months (IQR, 9.3–36.8) in the reduced dosage group, respectively.

Conclusions

The reduced dosage of 37.5 mg sunitinib tended to decrease toxicity and the incidences of severe AEs and treatment-related deaths. This reduced dosage regimen showed equivalent clinical efficacy including patient survival. The reduced dosage of 37.5 mg sunitinib can be adopted as an alternative therapy for patients with imatinib-resistant and/or intolerant GISTs.

DOI： 10.1093/jjco/hyac202

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Palliative chemotherapy is commonly used for advanced cancer patients. The timing of chemotherapy termination is crucial for efforts to maintain quality of life. PATIENTS AND METHODS: This retrospective study included gastrointestinal cancer patients who were treated with chemotherapy and died between 2013 and 2022 at Niigata University Medical and Dental Hospital. Data were reviewed regarding age, gender, cancer type, reason for chemotherapy termination, cause of death, survival after chemotherapy termination, and place of death. RESULTS: In total, 388 patients were included; the median survival after chemotherapy was 73 days. Patients aged <67 years had shorter survival durations (59 days), compared with patients aged >67 years (82 days). Ten (2.6%) patients began a new chemotherapy regimen, whereas 17 (4.4%) patients received chemotherapy, within 4 weeks before death. The most common reason for chemotherapy termination was disease progression, and most deaths occurred in hospitals. CONCLUSION: The rates of chemotherapy and initiation of new chemotherapeutic regimens near the end of life were lower than previously reported. Most deaths occurred in hospitals, highlighting the need for development of hospices.

DOI： 10.1089/pmr.2023.0027

PubMed

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Neuroendocrine neoplasms of the colon and rectum are colorectal epithelial neoplasms with neuroendocrine differentiation. A platinum regimen used for small cell lung cancer is the currently recommended chemotherapy for gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), regardless of the organ. The BRAF V600E mutation has been recently reported as a druggable driver mutation in colorectal NECs. In BRAF V600E mutant colorectal cancer, a combination of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody, with or without a MEK inhibitor, is recommended. Here, we report the case of 77-year-old man who had lymph node recurrence after surgery for primary ascending colonic NEC. Two cytotoxic regimens, cisplatin plus irinotecan and modified FOLFOX6, were administered as first- and second-line chemotherapies with no remarkable response observed. At this point, genetic analysis confirmed the tumor harbored a BRAF V600E mutation. Thus, a regimen of BRAF inhibitor plus anti-EGFR antibody was administered. After commencing this regimen, carcinoembryonic antigen levels decreased within normal range, and there was dramatic shrinkage of the lymph node metastases observed by chest and abdominal computed tomography scans. To our knowledge, this is the first reported case of a colorectal NEC responding to a BRAF inhibitor and anti-EGFR antibody.

DOI： 10.1007/s12328-022-01599-4

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Two patients underwent hemodialysis. Case 1 with stage IV gastric cancer was treated with reduced doses of capecitabine (1,000 mg/m2/day, days 1 to 14) and oxaliplatin (65 mg/m2, day 1). Although grade 1 thrombocytopenia occurred in the first cycle, grade 3 thrombocytopenia developed in the second cycle because of increasing dosage. After the dosage was reduced, chemotherapy was continued safely. Case 2 with stage IA gastroesophageal cancer was treated with radiotherapy followed by chemotherapy. Treatment with the same dose of CapeOX therapy as in case 1 resulted in no severe toxicity. We conclude that a half-dose of the CapeOX regimen is safe for gastric cancer patients undergoing hemodialysis.

DOI： 10.2169/internalmedicine.2718-19

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

The number of older patients with esophageal cancer (EC) is increasing due to the population aging and increasing life expectancy. However, no optimal treatment strategy for older patients with EC has been established to date. The aim of the present study was to review and compare the treatment modalities and outcomes of 990 younger and older patients diagnosed with EC in our institution. The patients were divided into younger (≤74 years) and older (≥75 years) groups. The majority of the patients in both groups had early-stage EC and were treated by endoscopic submucosal dissection (ESD). The older patients with locally advanced (stage II and III) EC were more likely to undergo chemoradiotherapy rather than esophagectomy. Among the older patients, 22% selected best supportive care. The disease-specific survival rate of the older patients was significantly lower compared with that of the younger patients, which was likely due to the less intense treatment modalities applied. The prognosis following esophagectomy was significantly better compared with that of chemoradiotherapy in the younger, but not in the older patients. In conclusion, the poorer prognosis of older patients (aged ≥75 years) with stage I EC may improve with multidisciplinary treatment after ESD. Although CRT is currently considered the optimal treatment for older patients with stage II/III EC, more efficient treatment modalities are urgently required.

DOI： 10.3892/mco.2019.1909

PubMed

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