Objective: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese.
Methods: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m for level 0, 80mg/m for level 1, and 100mg/m for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m, response rate, and incidences of adverse events.
Results: A CDDP dose of 100mg/m was the MTD for phase I, and the recommended dose for phase II was 80 mg/m. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event.
Conclusion: The present phase I study indicated that a CDDP dose of 80mg/m is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m as compared with a dose of 100mg/m, and a dose of 80mg/m is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.anl.2018.02.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chemotherapeutic hormesis induced by the tumor microenvironment in refractory ovarian cancer.
Sci Rep
January 2025
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
Advanced ovarian cancer often presents with multiple lesions exhibiting varying responses to chemotherapy, highlighting the critical influence of the tumor microenvironment (TME). This study investigates the phenomenon of chemotherapeutic hormesis, wherein low doses of chemotherapeutic agents, such as cisplatin (CDDP) and paclitaxel (PTX), paradoxically stimulate rather than inhibit cancer cell proliferation. Our findings indicate that NOS3 ovarian cancer cells, particularly drug-resistant variants, exhibit enhanced proliferation when exposed to low concentrations of these drugs.
View Article and Find Full Text PDFMulti-omics analysis reveals the protective effects of Chinese yam polysaccharide against cisplatin-induced renal interstitial fibrosis.
Phytomedicine
January 2025
Department of Pharmacy, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, PR China.
Background: Chinese yam polysaccharide (SYDT) has been reported to protect renal function and mitigate renal fibrosis in mice with diabetic nephropathy. Based on a multi-omics analysis, the objectives of this study were to determine the effect of SYDT on cisplatin (CDDP)-induced chronic renal interstitial fibrosis (RIF) and the underlying molecular mechanisms using an in vivo model.
Methods: Rats were intraperitoneally injected with a single dose of CDDP and then treated with SYDT or amifostine (AMF).
Design, synthesis and biological evaluation of biaryl amide derivatives as modulators of multi-drug resistance.
Eur J Med Chem
January 2025
School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:
Article Synopsis
- - The study highlights the challenge of multi-drug resistance (MDR) in cancer treatment, mainly due to the overexpression of ABC transporters like P-glycoprotein (P-gp), which affects the effectiveness of chemotherapy drugs.
- - Researchers explored the biaryl amide skeleton for potential agents to reverse MDR and identified a compound, D2, that significantly reversed resistance to drugs like paclitaxel and cisplatin in various cancer cell lines.
- - Compound D2 works by binding to P-gp, lowering its expression, and enhancing drug accumulation in cells, showing promise as a solution to combat MDR in cancer treatments.
Initial adjustments in the dosage and rest period of gemcitabine plus cisplatin therapy for patients with incurable biliary tract cancer based on baseline estimated glomerular filtration rate (eGFR) values may be crucial for treatment outcomes and the preservation of renal function.
J Gastrointest Oncol
October 2024
Department of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan.
Background: Gemcitabine (GEM) and cisplatin (CDDP) combination therapy (GC therapy) is the standard 1st-line regimen for incurable biliary tract cancers (BTCs). However, the correlation between dynamic changes in renal function and the outcomes of GC therapy remains unclear. This study aimed to clarify the association between renal function alterations and treatment outcomes after GC therapy.
View Article and Find Full Text PDFEfficacy of Paclitaxel and Cetuximab in Recurrent/Metastatic Oral Cancer Cases Following Superselective Intraarterial Chemoradiotherapy: A Retrospective Cohort Study.
Cancer Diagn Progn
November 2024
Department of Oral and Maxillofacial Surgery, The Nippon Dental University School of Life Dentistry at Niigata, Niigata, Japan.
Background/aim: The therapeutic efficacy of the paclitaxel (PTX) + cetuximab (Cmab) combination regimen was investigated in patients with recurrence or metastasis after superselective intraarterial chemoradiotherapy (SSIACRT) for oral cancer, and the safety was retrospectively examined.
Patients And Methods: All enrolled patients with advanced oral cancer or who had refused surgery over 10 years from December 2012 to December 2022 underwent SSIACRT for 6 to 9 weeks [cisplatin (CDDP): total 160-630 mg/m and radiotherapy: total 50-70 Gy]. Nine cases (tongue cancer, maxillary gingival cancer, and mandibular gingival cancer; three cases each) were subjected to PTX + Cmab therapy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!