Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck

J. B. Vermorken, L. Licitra, J. Stöhlmacher-Williams, A. Dietz, J. M. Lopez-Picazo, O. Hamid, A. M. Hossain, S. C. Chang, T. C. Gauler

Research output: Contribution to journalArticle

Abstract

Purpose Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN. Methods Patients received cetuximab 250 mg/m2 (loading dose: 400 mg/m2) days 1, 8 and 15; pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated. Results Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3%), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2%). Diagnoses included oropharynx (45.5%) and larynx (24.2%) cancers, with locoregional disease (51.5%) alone, or combined with distant metastases (48.5%). Median (m) PFS was 4.4 months (95% confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95% CI: 6.5, 13.1). Objective response rate was 29.3%; 23 patients had stable disease (39.7%). Drug-related grade 3/4 toxicities included neutropaenia (33.3%), fatigue (24.2%), anorexia (12.1%) and infection (10.6%). Five treatment-related deaths (7.6%) occurred. Conclusions Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.

Original languageEnglish
Pages (from-to)2877-2883
Number of pages7
JournalEuropean Journal of Cancer
Volume49
Issue number13
DOIs
Publication statusPublished - Sep 2013

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Pemetrexed
Cisplatin
Disease-Free Survival
Confidence Intervals
Therapeutics
Oropharynx
Laryngeal Neoplasms
Anorexia
Vitamin B 12
Platinum
Folic Acid
Fluorouracil
Fatigue
Cetuximab
Carcinoma, squamous cell of head and neck
Maintenance
Neoplasm Metastasis
Survival

Keywords

  • cell carcinoma
  • Cetuximab
  • Cisplatin
  • Head and neck squamous
  • Pemetrexed

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck. / Vermorken, J. B.; Licitra, L.; Stöhlmacher-Williams, J.; Dietz, A.; Lopez-Picazo, J. M.; Hamid, O.; Hossain, A. M.; Chang, S. C.; Gauler, T. C.

In: European Journal of Cancer, Vol. 49, No. 13, 09.2013, p. 2877-2883.

Research output: Contribution to journalArticle

Vermorken, JB, Licitra, L, Stöhlmacher-Williams, J, Dietz, A, Lopez-Picazo, JM, Hamid, O, Hossain, AM, Chang, SC & Gauler, TC 2013, 'Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck', European Journal of Cancer, vol. 49, no. 13, pp. 2877-2883. https://doi.org/10.1016/j.ejca.2013.05.002
Vermorken, J. B. ; Licitra, L. ; Stöhlmacher-Williams, J. ; Dietz, A. ; Lopez-Picazo, J. M. ; Hamid, O. ; Hossain, A. M. ; Chang, S. C. ; Gauler, T. C. / Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck. In: European Journal of Cancer. 2013 ; Vol. 49, No. 13. pp. 2877-2883.
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abstract = "Purpose Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN. Methods Patients received cetuximab 250 mg/m2 (loading dose: 400 mg/m2) days 1, 8 and 15; pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated. Results Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3{\%}), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2{\%}). Diagnoses included oropharynx (45.5{\%}) and larynx (24.2{\%}) cancers, with locoregional disease (51.5{\%}) alone, or combined with distant metastases (48.5{\%}). Median (m) PFS was 4.4 months (95{\%} confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95{\%} CI: 6.5, 13.1). Objective response rate was 29.3{\%}; 23 patients had stable disease (39.7{\%}). Drug-related grade 3/4 toxicities included neutropaenia (33.3{\%}), fatigue (24.2{\%}), anorexia (12.1{\%}) and infection (10.6{\%}). Five treatment-related deaths (7.6{\%}) occurred. Conclusions Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.",
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T1 - Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck

AU - Vermorken, J. B.

AU - Licitra, L.

AU - Stöhlmacher-Williams, J.

AU - Dietz, A.

AU - Lopez-Picazo, J. M.

AU - Hamid, O.

AU - Hossain, A. M.

AU - Chang, S. C.

AU - Gauler, T. C.

PY - 2013/9

Y1 - 2013/9

N2 - Purpose Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN. Methods Patients received cetuximab 250 mg/m2 (loading dose: 400 mg/m2) days 1, 8 and 15; pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated. Results Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3%), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2%). Diagnoses included oropharynx (45.5%) and larynx (24.2%) cancers, with locoregional disease (51.5%) alone, or combined with distant metastases (48.5%). Median (m) PFS was 4.4 months (95% confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95% CI: 6.5, 13.1). Objective response rate was 29.3%; 23 patients had stable disease (39.7%). Drug-related grade 3/4 toxicities included neutropaenia (33.3%), fatigue (24.2%), anorexia (12.1%) and infection (10.6%). Five treatment-related deaths (7.6%) occurred. Conclusions Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.

AB - Purpose Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN. Methods Patients received cetuximab 250 mg/m2 (loading dose: 400 mg/m2) days 1, 8 and 15; pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated. Results Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3%), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2%). Diagnoses included oropharynx (45.5%) and larynx (24.2%) cancers, with locoregional disease (51.5%) alone, or combined with distant metastases (48.5%). Median (m) PFS was 4.4 months (95% confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95% CI: 6.5, 13.1). Objective response rate was 29.3%; 23 patients had stable disease (39.7%). Drug-related grade 3/4 toxicities included neutropaenia (33.3%), fatigue (24.2%), anorexia (12.1%) and infection (10.6%). Five treatment-related deaths (7.6%) occurred. Conclusions Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.

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