Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck: results of the Yale Mitomycin Randomized Trials.

PURPOSE Two consecutive randomized trials were run at our institution using the bioreductive alkylating agent mitomycin as an adjunct to radiation therapy in an effort to improve outcome in patients with squamous cell carcinoma of the head and neck. METHODS Between 1980 and 1992, two consecutive randomized trials using mitomycin (trial 1) and mitomycin with dicumarol (trial 2) as an adjunct to radiation therapy in patients with squamous cell carcinoma of the head and neck were conducted at our institution. The patients were stratified by intent of therapy, extent of disease, and primary tumor site. Within each strata, patients were randomized to receive radiation therapy with or without mitomycin (trial 1) or mitomycin/dicumarol (trial 2). RESULTS A total of 203 patients were enrolled onto both trials, 195 of whom were eligible for analysis. Patients were equally balanced with respect to sex, age, extent of disease, primary site, radiation dose, and total duration of radiation treatment. Hematologic toxicities were more frequently noted in the drug-treated arms, but were acceptable with no drug-related treatment deaths. Nonhematologic toxicities were acceptable and not significantly different between the two arms. As of September 1995, with a median follow-up of 138 months, a statistically significant benefit occurred in the mitomycin arms with respect to cause-specific survival (0.74 +/- 0.05 v 0.51 +/- 0.05; P = .005), local recurrence-free survival (0.85 +/- 0.04 v 0.66 +/- 0.05; P = .002), and local regional recurrence-free survival (0.76 +/- 0.05 v 0.54 +/- 0.05; P = .003). No statistically significant difference in overall survival was obtained (0.48 +/- 0.05 mitomycin arms v 0.42 +/- 0.05 radiation alone). CONCLUSION The bioreductive alkylating agent mitomycin is a safe and effective adjunct to radiation therapy in the treatment of squamous cell carcinoma of the head and neck. The statistically and clinically significant improvement in local regional relapse and cause-specific survival obtained support the use of mitomycin as an adjunct to radiation therapy in the management of squamous cell carcinoma of the head and neck.

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Hyperfractionated Radiation Therapy With or Without Concurrent Low-Dose Daily Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Prospective Randomized Trial

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.7.1458 ◽

2000 ◽

Vol 18 (7) ◽

pp. 1458-1464 ◽

Cited By ~ 345

Author(s):

Branislav Jeremic ◽

Yuta Shibamoto ◽

Biljana Milicic ◽

Nebojsa Nikolic ◽

Aleksandar Dagovic ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Radiation Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Low Dose ◽

Locally Advanced ◽

Progression Free Survival ◽

High Grade ◽

Free Survival

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.

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Gemcitabine versus cisplatin concurrent with radiation therapy in locally advanced head and neck squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5557 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5557-5557

Author(s):

Magda Mostafa ◽

Hesham Atif ◽

Mahmoud Fawzy ◽

Amr Yehia Sakr ◽

Ahmed Alashwah

Keyword(s):

Squamous Cell Carcinoma ◽

Radiation Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Locally Advanced ◽

Progression Free Survival ◽

Advanced Head ◽

Free Survival ◽

Weekly Cisplatin

5557 Background: In locally advanced head and neck squamous cell carcinoma (HNSCC) weekly cisplatin concurrent with radiation therapy is the standared treatment. However some patients cannot tolerate cisplatin. So we conduct a prospective randomized trial comparing cisplatin versus gemcitabine. Methods: This trial was done in Kasr El-Ainy Center of Clinical Oncology and Radiation therapy (NEMROCK), during the period from March 2010 till June 2011. Sixty patients with locally advanced HNSCC were randomized to receive Cisplatin (30 mg/m2) weekly for 6 consecutive weeks (30 patients) or Gemcitabine (50 mg/m2) weekly for 6 consecutive weeks (30 patients) both concomitant with radiation therapy reaching a dose of 70 Gy over 7 weeks. Primary end points include response rate, progression free survival and toxicity. Toxicities were graded according to NCI-CTCAE v3.0. Results: Thewhole study group included 48 (80%) males and 12 (20%) females. Mean age was 47.9 (± 6.5) years (range 26-61). Both arms were comparable regarding their age, gender, performance status and stage. There were 9 (30%) CR, 7 (23.3%) PR, 2 (6.7%) SD and 12 (40%) PD in cisplatin arm versus 12 (40%) CR, 4 (13.3%) PR, 1 (3.3%) SD and 11 (36.7%) PD in gemcitabine arm. Median progression free survival (PFS) in cisplatin arm was 9 months versus 11months in gemcitabine arm with a hazard ratio of 0.08 (95% CI 0.005 – 1.47). We did not reach median overall survival. Radiotherapy induced skin toxicity (slight or patchy atrophy), nausea, vomiting, mucositis, salivary gland affection and weight loss were equally distributed in both arms. Dysphagia and fatigue were markedly higher in gemcitabine arm. While infection and neutropenia were slightly higher in cisplatin arm. Conclusions: Weekly gemcitabine 50mg/m2 concomitant with radiotherapy was found to be of equal efficacy and toxicity comparable with weekly cisplatin in the treatment of locally advanced HNSCC.

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Radiation Therapy With or Without Concurrent Low-Dose Daily Chemotherapy in Locally Advanced, Nonmetastatic Squamous Cell Carcinoma of the Head and Neck

Journal of Clinical Oncology ◽

10.1200/jco.2004.10.076 ◽

2004 ◽

Vol 22 (17) ◽

pp. 3540-3548 ◽

Cited By ~ 58

Author(s):

Branislav Jeremic ◽

Biljana Milicic ◽

Aleksandar Dagovic ◽

Zeljko Vaskovic ◽

Ljiljana Tadic

Keyword(s):

Squamous Cell Carcinoma ◽

Radiation Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Controlled Trial ◽

Locally Advanced ◽

Therapeutic Benefit ◽

Recurrence Free Survival ◽

Free Survival

Purpose To retrospectively investigate the difference between conventionally fractionated (CF) and hyperfractionated (Hfx) radiation therapy (RT), with and without either daily cisplatin (CDDP) or carboplatin (CBDCA), in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) enrolled onto two consecutive prospective randomized studies. Patients and Methods Treatment consisted of CF RT (70 Gy, group 1), CF RT and either daily CDDP (6 mg/m2) or daily CBDCA (25 mg/m2; group 2), Hfx RT (77 Gy, 1.1 Gy bid; group 3), or Hfx RT and daily CDDP (group 4). Results Hfx RT plus CDDP achieved better overall survival (OS) and local recurrence-free survival (LRFS) than any other group. There was an insignificant difference favoring Hfx RT over CF RT, either alone or in combination with CDDP or CBDCA, regarding both OS (P = .058 and P = .051, respectively) and LRFS (P = .088 and P = .091, respectively). No difference was seen between CF RT plus chemotherapy (CHT) and Hfx RT alone regarding either OS (P = .32) or LRFS (P = .48). Regional recurrence-free survival was similar in the four treatment groups. CF RT plus CHT and Hfx RT plus CDDP achieved better distant metastasis-free survival than CF RT and Hfx RT. High-grade toxicity was significantly more frequent in Hfx RT plus CDDP than in any other group, except in the Hfx RT group. Hfx RT led to significantly more acute toxicity and xerostomia than CF RT plus CHT. Hfx RT was more toxic than CF RT, either alone or with concurrent CHT. Conclusion Results of this study show that there may be a therapeutic benefit for CF RT plus CHT over Hfx RT plus CDDP in patients with SCCHN, but this cannot be firmly established without a larger and well-planned controlled trial.

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