Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

25 mg/m2/day IV infusion at D1 to D4, at D22 to D25, at D43 to D46 during the radiotherapy

100 mg/m2/day IV infusion at D1, D22 and D43 during the radiotherapy

25 mg/m2/day IV infusion at D1 to D4, at D22 to D25, at D43 to D46 during the radiotherapy.

Split Cisplatin

100 mg/m2/day IV infusion at D1, D22 and D43 during the radiotherapy.

70 Gy in 35 fractions of 2 Gy in non-operated patients and 66 Gy in 33 fractions in post-operative.

Radiotherapy

Christian BOREL, MD

The general aim is to compare the cumulative dose of cisplatin administered concomitantly with radiotherapy in reference arm A (cisplatin 100 mg / m2 day 1 every 21 days) and in the experimental arm B (Cisplatin split 25 mg / m2 / J D1 to D4 all 21 days).

The standard treatment for squamous cell carcinoma of the head and neck locally advanced non-operated or non-operable is a combination of radiotherapy and concomitant chemotherapy. Indeed, the meta-analysis MACH showed for RT / CT associations an absolute survival benefit of 8% compared with radiotherapy alone. Cisplatin delivered optimally, ie at a dose of 100 mg / m2 on day 1, D22 and D43 of radiotherapy is as effective as combinations of cisplatin and 5-fluorouracil.

In post operative, treatment of high risk recurrence forms by Cisplatin, concomitantly with radiotherapy, also increases local control and overall survival.

However, it is an association whose toxicity is significant. The usual limiting toxicities were mucositis, dysphagia, nausea and vomiting with malnutrition and biologically kidney failure and myelotoxicity. Only 2/3 of the patients receive 3 cycles of cisplatin initially programmed.

As shown in the RTOG 0129 trial, the number of cycles of cisplatin and thus the cumulative dose of cisplatin administered concurrently with radiation therapy, significantly influences the locoregional control, progression free survival and overall survival.

One method of reducing the toxicity and thereby, increase the cumulative dose, would be to split the administration of cisplatin.

Moreover, the efficacy of Cisplatin, which only the free fraction is active, seems correlated with AUC that peak plasma which would in turn responsible for toxicity. The completion of a pharmacokinetic study comparing the AUC and Cmax obtained with cisplatin 100 mg / m2 and cisplatin fractionated is essential.

Finally, the limiting renal toxicity induced by cisplatin is currently diagnosed using the creatinine clearance. The Neutrophil gelatinase-associated lipocalin (NGAL) urinary is a new diagnosis and prognosis marker of renal impairment following treatment with cisplatin. However, further studies are needed to validate its clinical utility.

Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion

Phase II Randomized Trial Comparating Two Concomitant Administration of Radiotherapy With Cisplatin in Patients With Not Operated or Inoperable HNSCC or With Recurrence High Risk in Adjuvant Postoperative Treatment

cisplatin dose amount received at each cycle

Assessment of toxicity in accordance with NCI-CTC-AE 4.03

Interruption of radiotherapy due to toxicity

Delay between the date of randomisation and the occurrence of a recurrence

Delay between the date of randomization and death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion	NCT03330249	Squamous Cell C...	Split Cisplatin Cisplatin Radiotherapy	18 Years - 70 Years	Groupe Oncologie Radiotherapie Tete et Cou
Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion	NCT03330249	Squamous Cell C...	Split Cisplatin Cisplatin Radiotherapy	18 Years - 70 Years	Groupe Oncologie Radiotherapie Tete et Cou

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