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Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer

Induktionschemotherapie, gefolgt von begleitender hyperfraktionierter Radiochemotherapie, bei lokal fortgeschrittenen Hals-Kopf-Karzinomen: Pilotstudie

A pilot study

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Abstract

Purpose

To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer.

Methods

A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2 in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m2).

Results

Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed.

Conclusions

High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer.

Zusammenfassung

Ziel

Bewertung der Durchführbarkeit der Induktionschemotherapie, gefolgt von begleitender hyperfraktionierter Radiotherapie und Chemotherapie, bei inoperablen, lokal fortgeschrittenen Hals-Kopf-Karzinomen.

Methoden

Es wurde eine Pilotstudie mit sechs Patienten durchgeführt: Sie umfaßte drei Zyklen mit cis-Platin (100 mg/m2, Tag 1) und 5-Fluorouracil (1000 mg/m2 in intravenöser Dauerinfusion während der ersten 120 Stunden), gefolgt von bifraktionierter Radiotherapie bis zu einer Dosis von 74,4 Gy auf Tumor und zervikale Lymphknotenmetastasen, verabreicht in zwei Dosen von 1,2 Gy pro Tag, fünf Tage pro Woche, kombiniert mit begleitender cis-Platin-Gabe (50 mg/m2 pro Woche).

Ergebnisse

Alle sechs Patienten beendeten die Protokolltherapie. Die am häufigsten aufgetretenen akuten Nebenwirkungen waren schwere Mukositis und Myelotoxizität, die bei allen fünf Patienten beobachtet wurden. Die akute Toxizität machte die Unterbrechung der begleitenden Chemotherapie in fünf Fällen erforderlich, und in zwei Fällen war die Aussetzung der Radiotherapie notwendig. Eine parenterale schmerzlindernde Therapie mit Morphium wurde bei vier Patienten durchgeführt, drei von ihnen mußten ins Krankenhaus eingewiesen werden. Ein Patient erlitt einen Tag nach Beendigung der Therapie einen Hirnschlag und verstarb sieben Tage später. Aufgrund der hohen akuten Toxizität wurde von der Aufnahme von weiteren Patienten in die Studie abgesehen. Nach einem durchschnittlichem Follow-up von 17 Monaten sind vier Patienten noch am Leben, drei von ihnen ohne Krankheitserscheinungen, während bei einem eine lokale Progression festzustellen ist.

Schlußfolgerungen

Die hohe akute Toxizität der Induktionstherapie mit cis-Platin und 5-Fluorouracil, gefolgt von begleitender hyperfraktionierter Radiotherapie und cis-Platin-Gabe, macht bei inoperablen, lokal fortgeschrittenen Kopf-Hals-Tumoren weniger toxische Behandlungsschemata erforderlich.

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Authors and Affiliations

  1. Division of Radiotherapy, European Institute of Oncology, Milan, Italy

    Barbara Jereczek-Fossa, Maria Cristina Leonardi, Hugo Raul Marsiglia & Roberto Orecchia

  2. Division of Medical Oncology, European Institute of Oncology, Milan, Italy

    Filippo De Braud, Maura Gasparetto & Tommaso De Pas

  3. Division of Head and Neck Surgery, European Institute of Oncology, Milan, Italy

    Nicoletta Tradati

  4. Department of Oncology and Radiotherapy of the Medical University of Gdansk, Poland

    Barbara Jereczek-Fossa

  5. Faculty of Medicine of the University of Milan, Italy

    Roberto Orecchia

Authors
  1. Barbara Jereczek-Fossa
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  2. Filippo De Braud
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  3. Maura Gasparetto
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  4. Tommaso De Pas
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  5. Nicoletta Tradati
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  6. Maria Cristina Leonardi
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  7. Hugo Raul Marsiglia
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  8. Roberto Orecchia
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Correspondence to Barbara Jereczek-Fossa.

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Jereczek-Fossa, B., De Braud, F., Gasparetto, M. et al. Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer. Strahlenther Onkol 174, 457–461 (1998). https://doi.org/10.1007/BF03038623

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  • DOI: https://doi.org/10.1007/BF03038623

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