Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

Schneider, M.; Etienne, Marie‐Christine; Milano, Gérard; Thyss, Antoine; Otto, Josiane; Dassonville, O.; Mobayen, H.; Saudes, Laurence; Guillot, T.; Démard, F

doi:10.1200/jco.1995.13.7.1656

Cited by 54 publications

(20 citation statements)

References 28 publications

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“…This is the reason why we emphasized the achievement of a CR as evidence of clinical activity, rather than looking at objective responses. The results obtained in this study are not substantially different from those of other trials of CDDP-5-FU-based regimens [17, 26], and our regimen seems unlikely to represent a major breakthrough when used in this setting. However, a recent meta-analysis [27]has shown that concomitant chemo-radiotherapy is likely to be the most suitable way forward for the treatment of patients with locally advanced, inoperable SCCHN.…”

Section: Discussionsupporting

confidence: 27%

Cisplatin, Raltitrexed, Levofolinic Acid and 5-Fluorouracil in Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck: A Phase II Randomized Study

Caponigro

Rosati

Rosa³

et al. 2002

Oncology

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Background: Cisplatin (CDDP) is among the most active single agents against squamous cell carcinoma of the head and neck (SCCHN), and it is still the reference drug in the induction chemotherapy setting, when used in combination with infusional 5-fluorouracil (5-FU). Raltitrexed has been shown to be devoid of clinical activity against SCCHN when used alone; however, both preclinical and early clinical data regarding the combination raltitrexed-CDDP hold promise. Thymidylate synthase is the target enzyme of both raltitrexed and 5-FU; however, the two drugs have distinct sites of action on the enzyme and the combination of the two agents may be synergistic. We have previously shown that the combination of raltitrexed, levofolinic acid (LFA) and 5-FU has clinical activity against SCCHN; in a subsequent phase I study, cisplatin was added, and the combination of CDDP plus raltitrexed on day 1, followed by LFA and 5-FU on day 2, was judged feasible and active, since a 67% response rate was shown across all dose levels, with a 100% response rate at the recommended dose for phase II. Methods: Patients with inoperable locally advanced or metastatic SCCHN, not pretreated with chemo- or radiotherapy were randomized to receive either CDDP 60 mg/m² and raltitrexed 2.5 mg/m² on day 1 and LFA 250 mg/m² and 5-FU 900 mg/m² on day 2 (arm A) or CDDP 65 mg/m² and methotrexate 500 mg/m² on day 1, and LFA 250 mg/m² and 5-FU 800 mg/m² on day 2 (arm B). Both treatments were repeated every 2 weeks. Evaluation for tumor response was performed after four cycles. According to Simon two-stage design, with a target complete response (CR) rate (p1) of 35%, at least 7 CR among the first 31 treated patients and 16 CR among the final sample size of 52 patients were required. Results: An interim analysis was performed when 36 patients were evaluable in each arm. In arm A, 10 CR (28%) and 19 partial responses (PR) (53%) were observed, for an overall response rate of 81%. In arm B, 3 CR (8%) and 12 PR (34%) were observed, for an overall response rate of 42%. The difference in both CR and overall response rate between the two arms was statistically significant (p = 0.03 and <0.001, respectively). Therefore, the accrual was stopped in arm B and continued only in arm A. Overall, 13 CR (21%) and 34 PR (56%) were observed among the 61 patients who were accrued in arm A, for an overall response rate of 77% (95% confidence interval 64–87%). Neutropenia was the main side effect in both arms (grade 3–4 in 45 and 23 patients in arm A and B, respectively). Extrahematologic toxicity was mild in both arms; however, 2 patients in arm B died due to toxicity (grade 4 mucositis in one case, grade 4 renal toxicity in the other). Conclusions: Although response data for our experimental treatment look encouraging, the hypothesis of a 35% activity, expressed as capability to induce a CR, cannot be accepted. The results obtained in this study are not substantially different from those...

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Section: Discussionsupporting

confidence: 27%

Cisplatin, Raltitrexed, Levofolinic Acid and 5-Fluorouracil in Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck: A Phase II Randomized Study

Caponigro

Rosati

Rosa³

et al. 2002

Oncology

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“…Moreover, several pharmacokinetic-pharmacodynamic studies have proven that the systemic exposure to 5-FU, usually expressed as the area under the concentration versus time curve (AUC), is correlated with both toxicity and tumor response. 13 In addition, dosage individualization requires a number of serum samples at least equal to the number of kinetic parameters to be determined, which is usually unfeasible in the daily clinical practice. Nevertheless, bayesian methods allow us to integrate clinical pharmacokinetic monitoring, using at least one plasma drug concentration, in the dayto-day management of oncologic patients.…”

Section: Introductionmentioning

confidence: 99%

A Bayesian Method for Predicting 5‐Fluorouracil Pharmacokinetic Parameters Following Short‐Term Infusion in Patients With Colorectal Cancer

Climente‐Martí

Merino-Sanjuán

Almenar-Cubells

et al. 2003

Journal of Pharmaceutical Sciences

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“…The dose-intensive cisplatin -5-FU -leucovorin (PFL) combination was subsequently developed in an attempt to improve complete response rates to induction chemotherapy and thus survival. The addition of leucovorin resulted in higher complete response rates at the expense of increased toxicity (Vokes et al, 1990;Schneider et al, 1995;Clark et al, 1997).…”

mentioning

confidence: 99%

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

Posner

Lefèbvre

2003

Br J Cancer

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Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin -5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel -PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and overall response rates were demonstrated across the phase II trials in the range 42 -82 and 71 -100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and overall response of patients treated with docetaxel-based induction chemotherapy.

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Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

Abstract: This study highlights the efficacy of CP/FU/l FA in head and neck carcinoma and establishes the clinical importance of coupled FU/FA pharmacokinetics to predict pharmacodynamic variability.

Cited by 54 publications

References 28 publications

Cisplatin, Raltitrexed, Levofolinic Acid and 5-Fluorouracil in Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck: A Phase II Randomized Study

Cisplatin, Raltitrexed, Levofolinic Acid and 5-Fluorouracil in Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck: A Phase II Randomized Study

A Bayesian Method for Predicting 5‐Fluorouracil Pharmacokinetic Parameters Following Short‐Term Infusion in Patients With Colorectal Cancer

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

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