A phase I–II study of concomitant chemoradiotherapy with paclitaxel (one-hour infusion), 5-fluorouracil and hydroxyurea with granulocyte colony stimulating factor support for patients with poor prognosis head and neck cancer

Brockstein, B.; Haraf, Daniel J.; Stenson, Kerstin; Sulzen, Laura; Witt, Mary Ellyn; Weichselbaum, Ralph; Vokes, Everett E.

doi:10.1023/a:1008324131519

Cited by 35 publications

(18 citation statements)

References 23 publications

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“…The TFGX regimen followed from our experience with TFHX (21,22). TFGX differs from TFHX in that gemcitabine was given instead of hydroxyurea.…”

Section: Discussionmentioning

confidence: 99%

“…The FHX (10 -12) and TFHX (20,21) regimens were initially studied in phase I trials in which patients with recurrent or second primary head and neck cancer (some previously irradiated), metastatic disease, poor prognosis, and/or poor anticipated survival were eligible. Eligibility criteria were the same in the present phase I trial, in which concurrent gemcitabine replaces hydroxyurea in TFHX regimen (TFGX regimen).…”

Section: Introductionmentioning

confidence: 99%

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Phase I Study of Concomitant Chemoradiotherapy with Paclitaxel, Fluorouracil, Gemcitabine, and Twice-Daily Radiation in Patients with Poor-Prognosis Cancer of the Head and Neck

Milano

Haraf

Stenson

et al. 2004

Clinical Cancer Research

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Purpose: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients.Experimental Design: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m 2 /d, for 5 days; paclitaxel, 100 mg/m 2 on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50 -300 mg/m 2 on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade >4 neutropenia or thrombocytopenia for >4 days; grade >4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed.Results: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m 2 during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m 2 delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common.Conclusions: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

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“…The TFGX regimen followed from our experience with TFHX (21,22). TFGX differs from TFHX in that gemcitabine was given instead of hydroxyurea.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phase I Study of Concomitant Chemoradiotherapy with Paclitaxel, Fluorouracil, Gemcitabine, and Twice-Daily Radiation in Patients with Poor-Prognosis Cancer of the Head and Neck

Milano

Haraf

Stenson

et al. 2004

Clinical Cancer Research

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“…A subsequent phase I study used paclitaxel, on day 1, only administered over 1 hour. This was shown to be feasible with a recommended phase II dose of paclitaxel of 100 mg/m 2 [24]. Tolerability was better than with the cisplatin-containing regimen, and hematologic toxicity was markedly lower than with the 120-hour infusion schedule.…”

Section: C-fhx and T-fhx Regimensmentioning

confidence: 99%

“…The regimen showed substantial locoregional activity, with objective response rates of more than 90% in both previously untreated and previously treated patients. This work led to additional phase I studies that suggested a role for chemoradiotherapy in locally recurrent disease [21][22][23][24].…”

Section: -Fu Hydroxyurea and Radiotherapymentioning

confidence: 99%

“…Both cisplatin and paclitaxel have been used as radiation enhancers in preclinical models and in the clinical setting against a variety of malignant tumors. The C-FHX and T-FHX regimens were evaluated in poor-prognosis patients in phase I trials that included pharmacological and clinical parameter evaluation [22][23][24]. In a phase I trial, cisplatin (100 mg/m 2 ) was added on every other cycle of FHX, that is, every 28 days, and hydroxyurea was escalated [22].…”

Section: C-fhx and T-fhx Regimensmentioning

confidence: 99%

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Intensive Concurrent Chemoradiotherapy for Head and Neck Cancer with 5-Fluorouracil- and Hydroxyurea-Based Regimens: Reversing a Pattern of Failure

et al. 2003

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Combined modality programs that were developed over the past two decades demonstrated that the nonsurgical therapy of locoregionally advanced head and neck cancer is feasible and produces survival outcomes that are at least comparable with surgery. The systemic therapy of head and neck cancer has gained momentum in recent years. Several randomized studies have shown that the concurrent administration of chemotherapy and radiation therapy is superior to radiation therapy alone. Medicine, 676 North St. Clair Street, Suite 850, Chicago, Illinois 60611, USA. Telephone: 312-695-6180; Fax: 312-695-6189; e-mail: aargiris@northwestern.edu Received December 10, 2002; accepted for publication April 21, 2003. ©AlphaMed Press 1083-7159/2003 The Oncologist ® LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the results of multicenter trials with chemoradiotherapy with 5-FU-and hydroxyurea-based regimens for the treatment of locoregionally advanced head and neck cancer.2. Explain the rationale for the combination treatment of radiation, 5-FU, and hydroxyurea.3. Recognize the toxicities and potential functional impairment for patients treated with aggressive concurrent chemoradiotherapy.4. Discuss the experimental role of induction chemotherapy in the management of locoregionally advanced head and neck cancer.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.

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Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation

Choe

Haraf

Solanki

et al. 2011

Cancer

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BACKGROUND: It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT. METHODS: The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor‐prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5‐fluorouracil, hydroxyurea, and a third agent. RESULTS: One hundred sixty‐six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow‐up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2‐year rates for OS, disease‐free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty‐three patients (19.9%) died of treatment‐related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2‐year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full‐dose ReRT, and radiotherapy interval. CONCLUSIONS: CReRT achieved a long‐term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients. Cancer 2011;. © 2011 American Cancer Society.

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A phase I–II study of concomitant chemoradiotherapy with paclitaxel (one-hour infusion), 5-fluorouracil and hydroxyurea with granulocyte colony stimulating factor support for patients with poor prognosis head and neck cancer

Cited by 35 publications

References 23 publications

Phase I Study of Concomitant Chemoradiotherapy with Paclitaxel, Fluorouracil, Gemcitabine, and Twice-Daily Radiation in Patients with Poor-Prognosis Cancer of the Head and Neck

Phase I Study of Concomitant Chemoradiotherapy with Paclitaxel, Fluorouracil, Gemcitabine, and Twice-Daily Radiation in Patients with Poor-Prognosis Cancer of the Head and Neck

Intensive Concurrent Chemoradiotherapy for Head and Neck Cancer with 5-Fluorouracil- and Hydroxyurea-Based Regimens: Reversing a Pattern of Failure

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation

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