Docetaxel, ifosfamide and cisplatin (DIP) in squamous cell carcinoma of the head and neck.
ABSTRACT Docetaxel, ifosfamide and cisplatin have all shown activity in squamous cell carcinoma of the head and neck (SCCHN). The optimal combination of the three drugs is, however, unknown. Considering the favorable results of taxane-containing triplets as induction chemotherapy in locally advanced (LA) SCCHN, DIP (docetaxel, ifosfamide, cisplatin) was studied in this setting as part of a phase I dose- and sequence-exploring study.
D (60 or 75 mg/m(2)) was given by 60-min infusion on day 1, I (1000 mg/m(2)/day), with mesna until 12 hours after I, by 24-h infusion days 1-5, and P (50 or 75 mg/m(2)) by 24-h infusion on days 1 or 5. The cycles were repeated every 21 days. Toxicities according to the National Cancer Institute Common Toxicity Criteria version 2 (NCI-CTC2) were evaluated weekly and response was evaluated every 2 cycles according to the World Health Organization (WHO) criteria. Thereafter, radiotherapy (RT, cumulative dose 70 Gy) or chemoradiation (CRT), both with conventional fractionation, were planned.
Twenty-two patients (18 male, 4 female; age 41-66 years, performance status 0-1, 2 T4N0, 3 T3N2, 11 T4N2, 3 T unknown N3, 1 T1N3 and 2 T4N3) received a median of 4 DIP cycles (range 1-5). Grade 4 neutropenia occurred in 18 patients, grade 3 and 4 thrombocytopenia in 5 and 1 patients, respectively, and grade 3 anemia in 5 patients. Gastrointestinal and mucosal toxicities were generally mild/moderate. Vascular complications (probably not DIP-related) precluded local treatment in two patients. Moreover, one patient died on day 13 of the first DIP (neutropenic sepsis and myocardial infarction). The remaining patients received RT (n=2) or CRT (n=17; 16 of these with gemcitabine). The response to 2 x DIP was 95% (1 complete response, 19 partial responses, 1 stable disease); the complete response rate increased to 42% after 4 x DIP. No dose or sequence effect was evident. The minimum follow-up of the surviving patients was 51 months, with median relapse-free survival of 13.8 months and median overall survival of 18.8 months. Only four patients relapsed at distant sites.
DIP is highly active in previously untreated LA SCCHN, however, toxicity of DIP in this population is substantial.
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ABSTRACT: While a large proportion of patients presenting with stage I and II squamous cell carcinoma of the head and neck (SCCHN) will remain disease free after single modality treatment, the majority of patients presenting in a more advanced disease stage and very often treated with a form of combined modality treatment, will eventually relapse, either locoregionally only, at distant sites only or both. A few patients with a locoregional recurrence can be salvaged by surgery or reirradiation. However, most patients with recurrent or metastatic (R/M) disease only qualify for palliative treatment. Treatment options in these patients include supportive care only, or in addition single agent chemotherapy, combination chemotherapy or targeted therapies either alone or in combination with cytotoxic agents. Prognostic factors analysis in such patients treated with (platinum-based) chemotherapy has identified five adverse prognostic factors, which seems worthwhile to take into consideration when performing trials; one pathologic feature (tumor cell differentiation) and four clinical baseline characteristics (ECOG performance status, weight loss, location of the primary tumor and prior radiotherapy). Moreover, it has been shown that response to systemic therapy has a major impact on survival. None of the trials performed in the past, even those with a reasonable sample size, have shown that aggressive platinum-based combination chemotherapy leads to survival benefit when compared to single agent methotrexate, cisplatin or 5-fluorouracil. After decades without real progress, a recent European randomized trial showed that adding cetuximab, the first clinically available EGFR-directed monoclonal antibody, to a standard chemotherapy regimen (platinum/5-fluorouracil) leads to an important survival benefit and this, with support of an additional smaller study in the US, has changed practice.Annals of Oncology 10/2010; 21 Suppl 7:vii252-61. · 7.38 Impact Factor
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ABSTRACT: To test the efficacy and safety of a triweekly reduced-dose docetaxel (60 mg/m(2)) regimen combined with a standard dose of cisplatin in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Patients with R/M HNSCC were enrolled. All eligible patients received intravenous docetaxel 60 mg/m(2) combined with cisplatin 75 mg/m(2) on day 1 and then every 3 weeks thereafter. Treatment was continued until disease progression, patient intolerance, or death. In total, 58 patients were enrolled and 41 patients were evaluated. Among the evaluated population, one patient achieved a complete response (2.4%) and nine patients achieved a partial response (22%), resulting in an overall response rate of 24.4%. Furthermore, 17 patients had stable disease (41.5%), which corresponds to a disease control rate of 65.9%. With a median follow-up of 24 months (1-43 months), progression-free survival was 170 days (95% confidence interval 97.9-242.1) and the median overall survival was 265 days (95% confidence interval 89.0-441.0) in evaluable population. The most common toxicities (≥ grade III) were leucopenia (66.7%) and anemia (33.3%). Triweekly reduced-dose docetaxel 60 mg/m(2) combined with cisplatin is effective and feasible for Taiwanese patients with R/M HNSCC. However, the hematologic toxicity of this regimen should be carefully monitored and managed.Cancer Chemotherapy and Pharmacology 04/2011; 68(6):1477-84. · 2.80 Impact Factor