Concomitant Radiotherapy and Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer Definitive results of a phase I-II study

Orecchia, Roberto; Ragona, Riccardo; Airoldi, Mario; Gabriele, P.; Gribaudo, Sergio; Redda, Maria Grazia Ruo; Bussi, Mario; Cavalot, A; Rampino, Monica; Sannazzari, G.L.

doi:10.3109/02841869409083933

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…The one-and 2-year local-regional control rates were 64% and 53%, respectively; the oneand 2-year survival rates were 71% and 53%, respectively. Grade 3 and 4 mucositis was observed in 25-30% of patients, according to carboplatin dose level, grade 3 leukopenia in 5-10% and grade 3 thrombocytopenia in 2% 27 . Such results were comparable with other published data.…”

Section: Discussionmentioning

confidence: 97%

“…In an attempt to improve local control and survival in patients with advanced unresectable stage III and IV HNSCC and based on the results of a previous dose escalation study 27 , we undertook a prospective multicen-tric randomized trial of conventional radiotherapy alone or combined with daily low-dose carboplatin between 1992 and 1995. The final results of the trial, with a follow-up of up to 10 years, are reported herein.…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy Alone or with Concomitant Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer: Definitive Results of a Phase III Study with a Follow-Up Period of up to Ten Years

Redda

Ragona

Ricardi

et al. 2010

Tumori

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Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial. Materials and methods From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin. Results The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04). Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Radiotherapy Alone or with Concomitant Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer: Definitive Results of a Phase III Study with a Follow-Up Period of up to Ten Years

Redda

Ragona

Ricardi

et al. 2010

Tumori

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“…Another dose-limiting acute toxicity was neutropenia that was higher than that observed with carboplatin alone at a higher dose. 2 Due to toxicities to mucosa and to neutrophils, the MTD was 0.5 of CBCDA and 20 mg/m 2 of DTX. The chronic toxicities were not severe even if a percentage of patients were not fully functional at completion of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…In previous work, we have shown the feasibility and good tolerance of daily low-dose carboplatin (CBCDA) concomitant with conventional radiotherapy, 2 and in a randomized trial this concurrent chemotherapy offered improved disease-free and overall survival in stage III-IV HNC. 3 Docetaxel (DTX) has demonstrated significant activity and was well tolerated in the treatment of advanced HNC.…”

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confidence: 99%

Docetaxel, Carboplatin and Concomitant Radiotherapy for Unresectable Squamous Cell Carcinoma of the Head and Neck

Airoldi¹,

Cattel²,

Cortesina³

et al. 2004

American Journal of Clinical Oncology

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Concomitant chemoradiotherapy is the most effective treatment of unresectable head and neck cancer. Docetaxel and carboplatin are two active drugs that potentiate radiotherapy. Thirty patients (median age = 56 years; median Eastern Cooperative Oncology Group performance status = 1) received radiotherapy (70 Gy, 2 Gy/d, 5 d/wk) concurrent with carboplatin AUC 0.3 to 0.5 on day 1-5, weeks 1, 3, 5, 7, and docetaxel 15 to 25 mg/m2 on day 4 of weeks 2, 4, and 6. Site of unresectable squamous cell carcinoma was as follows: oropharynx, 41%; hypopharynx, 27%; oral cavity, 16%; and larynx, 16%. Stage was III in 13% and IV in 87%. In 11 patients, pharmacokinetic parameters were evaluated. Acute G4 toxicity was as follows: neutropenia, 20%; mucositis, 33%. We had the following acute G3 toxicities: mucositis, 40%; neutropenia, 37%; dermatitis, 23%; and anemia, 13%. The maximum tolerated dosage was area under the curve 0.5 for carboplatin and 20 mg/m2 for docetaxel. Median radiotherapy dose was 69 Gy, and 175 out of 210 courses (83%) were administered. At the end of the treatment, we had 20 complete responses (CR) (67%), 9 partial responses (30%), and 1 no change (3%). After radial neck dissection, 2 patients achieved a CR (overall CR = 73%). After a median follow-up of 2.5 years, we had a 3-year local progression-free survival of 85%, failure-free survival of 69%, and overall survival of 60%. A significant increase of Cmax of carboplatin concentration was noted at the beginning of weeks 3, 5, and 7. Total plasma platinum raises during each course of 5 days of carboplatin without reaching a steady state. Carboplatin, docetaxel, and concomitant conventional radiotherapy is a feasible and effective treatment of unresectable head and neck cancer. The concurrent administration of two drugs does not alter pharmacokinetic drug behavior compared with single-agent data.

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“…In this regard, although the key mechanism of the RT/DDP interaction is considered to lethally affect damage repair (Orrecchia et al, 1994), inhibition of sub-lethal damage repair, selective radiosensitization of hypoxic cells and other mechanisms may also play important roles (Pajak et al, 1991). Laboratory data showed that the DDP-enhanced RT-effect is more pronounced when drug is present in target cells during irradiation (SchaakeKonig et al, 1992), especially when fractionated schedules are used (Schwachofer et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and mucosal toxicity of concomitant chemo-radiotherapy in patients with locally-advanced squamous cell carcinoma of the head-and-neck in the light of a novel mathematical model

Strigari

Pinnarò²,

Carlini³

et al. 2016

Critical Reviews in Oncology/Hematology

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Background: In the last several decades, combined radiotherapy (RT) and chemotherapy (CT) have beenrecognized as feasible in locally-advanced-squamous-cell-carcinoma of the head-and-neck (LA-HNSCC).Several meta-analyses identified concurrent RT + CT (CRT) most likely effective approach respect toRT-alone. However, radiobiological models comparing different chemotherapeutic schedules againstdelivered RT fractionation schedule for overall survival and toxicity are still needed.Methods and materials: Based on 9 randomized trials (2785 patients), radiobiological models andmultivariate logistic regression model were used to derive dose-response curves and estimate the 5-year-overall survival (OS) and ≥G3 acute mucositis rate of CRT or RT-alone.Results: Equivalent dose at 2 Gy/fraction (EQD2) was calculated using the linear quadratic model. Theeffect of CRT schedules, considering the CT type and its administration schedule and the HPV status oftumors were estimated using the univariate/multivariate logistic regression. The multivariate logisticregression model for 5y-OS indicated EQD2 and the type of CT, the chemo-sensitization fraction and theHPV status significant prognostic factors, while for toxicity both EQD2 and the concomitant adminis-tration of 5-fluorouracil (5Fu) resulted as significant prognostic factors. Combined schedules cisplatin(DDP)+/−5Fu + RT produced the higher OS compared with combined carboplatin+/−5Fu + RT or RT-alone

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Concomitant Radiotherapy and Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer Definitive results of a phase I-II study

Cited by 8 publications

References 18 publications

Radiotherapy Alone or with Concomitant Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer: Definitive Results of a Phase III Study with a Follow-Up Period of up to Ten Years

Radiotherapy Alone or with Concomitant Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer: Definitive Results of a Phase III Study with a Follow-Up Period of up to Ten Years

Docetaxel, Carboplatin and Concomitant Radiotherapy for Unresectable Squamous Cell Carcinoma of the Head and Neck

Efficacy and mucosal toxicity of concomitant chemo-radiotherapy in patients with locally-advanced squamous cell carcinoma of the head-and-neck in the light of a novel mathematical model

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