Carboplatin in combination with weekly Paclitaxel as first-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma unfit to EXTREME schedule

Pêtre, Adeline; Dalban, Cécile; Karabajakian, Andy; Neidhardt, Ève-Marie; Roux, P.-E.; Poupart, M.; Deneuve, Sophie; Zrounba, Philippe; Fayette, Jérôme

doi:10.18632/oncotarget.25157

Cited by 18 publications

(15 citation statements)

References 27 publications

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“…There are, however, limited treatment options for these patients with the recurrent and/or metastatic situation, and chemotherapy is indicated [4]. Of note, platinum-based therapy such as platinum in combination with 5-fluorouracil and cetuximab is currently given as first-line regimen for recurrent and/or metastatic head and neck cancer [5,6]. But platinumbased regimens have a dismal prognosis and increase toxicity [7,8].…”

Section: Introductionmentioning

confidence: 99%

Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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To evaluate the safety and efficacy of novel cobalt complex with sulindac (Co-SLD), the zebrafish and oral squamous cell carcinoma CAL27 were investigated in the present study. The developmental toxicity of Co-SLD ranging from 5 to 20 lM was determined by exposure to 3-144-h post-fertilization (hpf) zebrafish. Our data showed that Co-SLD did not cause to the appreciable toxicity at low concentration (5 and 10 lM). A remarkable toxicity was observed at high concentration (20 lM), including increased mortality and malformation, delayed hatchability, reduced heart rate as well as suppressed behaviour. With regard to the antitumor activity of Co-SLD, inhibited cell growth and migration capability were outstandingly observed in oral squamous cell carcinoma treated with 10 and 20 lM Co-SLD, which could be mainly attributed to the Co-SLD-elicited mitochondrial damage as marked by the depression of mitochondrial membrane potential, ROS accumulation and ATP depletion. Furthermore, administration of 10 lM Co-SLD was an optimal concentration not only to avoid the normal tissue toxicity, but also to enhance the killing of cancer cells via disrupting mitochondrial dysfunction. Taken together the above results demonstrated the desirable response of oral squamous cell carcinoma to Co-SLD. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Pêtre et al. reported on a weekly paclitaxel and carboplatin combination in a particularly frail and heavily pretreated population that produced a 40% ORR, a median PFS of 4.7 months, and a median OS of 9.1 months ( 11 ). Interestingly, this study confirms the major impact of cisplatin eligibility and ECOG-PS on survival outcomes: median OS is 13.7 months for cisplatin-eligible patients whereas it is only 8 months for cisplatin-ineligible patients.…”

Section: Discussionmentioning

confidence: 99%

Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients

Carinato

Burgy

Ferry³

et al. 2021

Front. Oncol.

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ObjectiveFor most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety.MethodsWe reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0–2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety.ResultsWe identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8–55.8), and disease control rate was 65% (95% CI, 52.9–77.1). With a median follow-up of 35.7 months (IQR 28.6–48.8), median PFS was 5.8 months (95% CI, 4.5–7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0–1 patients, median OS was 14.8 months (95% CI, 12.2–21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III–IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders.ConclusionThe weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.

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“…Therefore, cetuximab was evaluated in combination with different platinum-based regimens [ 15 , 16 ]. Several retrospective and prospective studies have examined first-line chemotherapy based on a weekly combination of paclitaxel and cetuximab in R/M-HNSCCs, showing promising activity [ 11 , 17 , 18 ]. This schedule has proven to be a relevant therapeutic option for patients with poor prognosis considered unsuitable for the EXTREME regimen [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Pêtre et al evaluated the activity and safety of the weekly carboplatin and paclitaxel chemotherapy in patients with R/M HNSCC unfit for cisplatin due to comorbidities and poor baseline clinical condition. Weekly chemotherapy was efficient and well tolerated in this subgroup of particularly fragile patients [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…A large proportion of patients with R/M HNSCC have poor clinical conditions, weight loss, signs and symptoms related to the extent of the cancer such as pain or obstruction, comorbidities and impaired organ function, therefore they are not suitable for EXTREME treatment due to the high risk of developing high grade toxicity. Conversely, a weekly chemotherapy regimen plus cetuximab was considered a reliable therapeutic strategy in frail cancer patients with R/M-HNSCC [ 11 ]. Weekly taxane-based chemotherapy has proved to control cancer growth and its related symptoms, with reduced toxicity and with an appropriate safety profile [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era

et al. 2021

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Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.

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Carboplatin in combination with weekly Paclitaxel as first-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma unfit to EXTREME schedule

Cited by 18 publications

References 27 publications

Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients

Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era

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