Dataset Information

Combination of taxanes, cisplatin and fluorouracil as induction chemotherapy for locally advanced head and neck cancer: a meta-analysis.

ABSTRACT:

Background

Some investigations have suggested that induction chemotherapy with a combination of taxanes, cisplatin and fluorouracil (TPF) is effective in locally advanced head and neck cancer. However, other trials have indicated that TPF does not improve outcomes. The objective of this study was to compare the efficacy and safety of TPF with a cisplatin and fluorouracil (PF) regimen through a meta-analysis.

Methods

Four randomized clinical trials were identified, which included 1,552 patients with locally advanced head and neck cancer who underwent induction chemotherapy with either a TPF or PF protocol. The outcomes included the 3-year survival rate, overall response rate and different types of adverse events. Risk ratios (RRs) and their 95% confidence intervals (CIs) were pooled using RevMan 5.1 software.

Results

The 3-year survival rate (51.0% vs. 42.4%; p = 0.002), 3-year progression-free survival rate (35.9% vs. 27.2%; p = 0.007) and overall response to chemotherapy (72.9% vs. 62.1%; p<0.00001) of the patients in the TPF group was statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia (7.0% vs. 3.2%; p = 0.001) and alopecia (10.8% vs. 1.1%; p<0.00001) was higher in the TPF group.

Conclusion

The TPF induction chemotherapy regimen leads to a significant survival advantage with acceptable toxicity rates for patients with locally advanced head and neck cancer compared with the PF regimen.

SUBMITTER: Qin H

PROVIDER: S-EPMC3517538 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Combination of taxanes, cisplatin and fluorouracil as induction chemotherapy for locally advanced head and neck cancer: a meta-analysis.

Qin Hao H Luo Jie J Zhu Yuan-Ping YP Xie Hai-Li HL Yang Wei-Qiang WQ Lei Wen-Bin WB

PloS one 20121207 12

<h4>Background</h4>Some investigations have suggested that induction chemotherapy with a combination of taxanes, cisplatin and fluorouracil (TPF) is effective in locally advanced head and neck cancer. However, other trials have indicated that TPF does not improve outcomes. The objective of this study was to compare the efficacy and safety of TPF with a cisplatin and fluorouracil (PF) regimen through a meta-analysis.<h4>Methods</h4>Four randomized clinical trials were identified, which included 1 ...[more]

PMID: 23236511

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Project description:BackgroundIt is a major clinical challenge to predict which patients, with advanced stage head and neck squamous cell carcinoma, will not exhibit a reduction in tumor size following induction chemotherapy in order to avoid toxic effects of ineffective chemotherapy and delays for instituting other therapeutic options. Further, it is of interest to know to what extent a gene signature, which identifies patients with tumors that will not respond to a particular induction chemotherapy, is applicable when additional chemotherapeutic agents are added to the regimen.Methodology/principal findingsTo identify genes that predict tumor resistance to induction with cisplatin/5-fluorouracil (PF) or PF and a taxane, we analyzed patient tumor biopsies with whole genome microarrays and quantitative reverse transcriptase-PCR (TLDA) cards. A leave one out cross-validation procedure allowed evaluation of the prediction tool. A ten-gene microarray signature correctly classified 12/13 responders and 7/10 non-responders to PF (92% specificity, 82.6% accuracy). TLDA analysis (using the same classifier) of the patients correctly classified 12/12 responders and 8/10 non-responders (100% specificity, 90.9% accuracy). Further, TLDA analysis correctly predicted the response of 5 new patients and, overall, 12/12 responders and 13/15 non-responders (100% specificity, 92.6% accuracy). The protein products of the genes constituting the signature physically associate with 27 other proteins, involved in regulating gene expression, constituting an interaction network. In contrast, TLDA-based prediction (with the same gene signature) of responses to induction with PF and either of two taxanes was poor (0% specificity, 25% accuracy and 33.3% specificity, 25% accuracy).Conclusions/significanceSuccessful transfer of the microarray-based gene signature to an independent, PCR-based technology suggests that TLDA-based signatures could be a useful hospital-based technology for determining therapeutic options. Although highly specific for tumor responses to PF induction, the gene signature is unsuccessful when taxanes are added. The results illustrate the subtlety in developing "personalized medicine".

Project description:At a minimum follow-up of 2 years, the TAX 324 study showed a significant survival benefit of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in locally advanced head and neck cancer. We report the long-term results at 5 years' minimum follow-up.TAX 324 was a randomised, open-label phase 3 trial comparing three cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2), followed by intravenous cisplatin 100 mg/m(2) and fluorouracil 1000 mg/m(2) per day, administered as a continuous 24-h infusion for 4 days) with three cycles of PF (intravenous cisplatin 100 mg/m(2), followed by fluorouracil 1000 mg/m(2) per day as a continuous 24-h infusion for 5 days) in patients with stage III or IV squamous-cell carcinoma of the head or neck. Both regimens were followed by 7 weeks of chemoradiotherapy with concomitant weekly carboplatin. Randomisation was done centrally with the use of a biased-coin minimisation technique. At study entry, patients were stratified according to the site of the primary tumour, nodal status (N0 or N1 vs N2 or N3), and institution. For this long-term analysis, data as of Dec 1, 2008, were gathered retrospectively from patients' medical records. Overall and progression-free survival were the primary endpoints. Tracheostomy and dependence on a gastric feeding tube were used as surrogate measures for treatment-related long-term toxicity. The intention-to-treat analysis included data from all 501 patients (255 TPF, 246 PF); data from the initial analysis in 2005 were used for 61 patients who were lost to follow-up. TAX 324 was registered at ClinicalTrials.gov, NCT00273546.Median follow-up was 72·2 months (95% CI 68·8-75·5). Overall survival was significantly better after treatment with TPF versus PF (hazard ratio [HR] 0·74, 95% CI 0·58-0·94), with an estimated 5-year survival of 52% in patients treated with TPF and 42% in those receiving PF. Median survival was 70·6 months (95% CI 49·0-89·0) in the TPF group versus 34·8 months (22·6-48·0) in the PF group (p=0·014). Progression-free survival was also significantly better in patients treated with TPF (median 38·1 months, 95% CI 19·3-66·1, vs 13·2 months, 10·6-20·7; HR 0·75, 95% CI 0·60-0·94). We detected no significant difference in dependence on gastric feeding tubes and tracheostomies between treatment groups. In the TPF group, three (3%) of 91 patients remained feeding-tube dependent, compared with eight (11%) of 71 patients in the PF group. Six (7%) of 92 patients had tracheostomies in the TPF group, versus eight (11%) of 71 in the PF group.Induction chemotherapy with TPF provides long-term survival benefit compared with PF in locally advanced head and neck cancer. Patients who are candidates for induction chemotherapy should be treated with TPF.Sanofi-Aventis.

Project description:BackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32-71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

Dataset Information

Combination of taxanes, cisplatin and fluorouracil as induction chemotherapy for locally advanced head and neck cancer: a meta-analysis.

Background

Methods

Results

Conclusion

Publications

Combination of taxanes, cisplatin and fluorouracil as induction chemotherapy for locally advanced head and neck cancer: a meta-analysis.

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