Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC)

M. G. Fury, E. J. Sherman, Shyam Rao, S. Wolden, S. Smith-Marrone, B. Mueller, K. K. Ng, P. R. Dutta, D. Y. Gelblum, J. L. Lee, R. Shen, S. Kurz, N. Katabi, S. Haque, N. Y. Lee, D. G. Pfister

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. Patients and methods: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m2), given with standard weekly cetuximab (450 mg/m2 loading dose followed by 250 mg/m2 weekly) and concurrent IMRT (total dose, 70 Gy). Results: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m2) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m2), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). Conclusion: The recommended phase II dose for nab-paclitaxel is 60 mg/m2 weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone.

Original languageEnglish (US)
Article numbermdt579
Pages (from-to)689-694
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

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Radiotherapy
Taxoids
Mucositis
Maximum Tolerated Dose
Mouth
Confidence Intervals
Lymphopenia
Oropharynx
Induction Chemotherapy
Supraventricular Tachycardia
Survival
Maxillary Sinus
Larynx
Pharynx
Carcinoma, squamous cell of head and neck
130-nm albumin-bound paclitaxel
Cetuximab
Dehydration
Anemia
Neck

Keywords

  • Cetuximab
  • Head and neck
  • Nab-paclitaxel
  • Radiation
  • Squamous

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC). / Fury, M. G.; Sherman, E. J.; Rao, Shyam; Wolden, S.; Smith-Marrone, S.; Mueller, B.; Ng, K. K.; Dutta, P. R.; Gelblum, D. Y.; Lee, J. L.; Shen, R.; Kurz, S.; Katabi, N.; Haque, S.; Lee, N. Y.; Pfister, D. G.

In: Annals of Oncology, Vol. 25, No. 3, mdt579, 01.03.2014, p. 689-694.

Research output: Contribution to journalArticle

Fury, MG, Sherman, EJ, Rao, S, Wolden, S, Smith-Marrone, S, Mueller, B, Ng, KK, Dutta, PR, Gelblum, DY, Lee, JL, Shen, R, Kurz, S, Katabi, N, Haque, S, Lee, NY & Pfister, DG 2014, 'Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC)', Annals of Oncology, vol. 25, no. 3, mdt579, pp. 689-694. https://doi.org/10.1093/annonc/mdt579
Fury, M. G. ; Sherman, E. J. ; Rao, Shyam ; Wolden, S. ; Smith-Marrone, S. ; Mueller, B. ; Ng, K. K. ; Dutta, P. R. ; Gelblum, D. Y. ; Lee, J. L. ; Shen, R. ; Kurz, S. ; Katabi, N. ; Haque, S. ; Lee, N. Y. ; Pfister, D. G. / Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC). In: Annals of Oncology. 2014 ; Vol. 25, No. 3. pp. 689-694.
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abstract = "Background: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. Patients and methods: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m2), given with standard weekly cetuximab (450 mg/m2 loading dose followed by 250 mg/m2 weekly) and concurrent IMRT (total dose, 70 Gy). Results: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m2) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m2), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100{\%}, functional mucositis 65{\%}, and pain in throat/oral cavity 52{\%}. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65{\%} [95{\%} confidence interval (CI) 42{\%} to 81{\%}] and 2-year overall survival (OS) is 91{\%} (95{\%} CI 69-97). Conclusion: The recommended phase II dose for nab-paclitaxel is 60 mg/m2 weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone.",
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T1 - Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC)

AU - Fury, M. G.

AU - Sherman, E. J.

AU - Rao, Shyam

AU - Wolden, S.

AU - Smith-Marrone, S.

AU - Mueller, B.

AU - Ng, K. K.

AU - Dutta, P. R.

AU - Gelblum, D. Y.

AU - Lee, J. L.

AU - Shen, R.

AU - Kurz, S.

AU - Katabi, N.

AU - Haque, S.

AU - Lee, N. Y.

AU - Pfister, D. G.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Background: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. Patients and methods: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m2), given with standard weekly cetuximab (450 mg/m2 loading dose followed by 250 mg/m2 weekly) and concurrent IMRT (total dose, 70 Gy). Results: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m2) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m2), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). Conclusion: The recommended phase II dose for nab-paclitaxel is 60 mg/m2 weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone.

AB - Background: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. Patients and methods: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m2), given with standard weekly cetuximab (450 mg/m2 loading dose followed by 250 mg/m2 weekly) and concurrent IMRT (total dose, 70 Gy). Results: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m2) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m2), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). Conclusion: The recommended phase II dose for nab-paclitaxel is 60 mg/m2 weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone.

KW - Cetuximab

KW - Head and neck

KW - Nab-paclitaxel

KW - Radiation

KW - Squamous

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