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Phase I Study of Docetaxel (D), Cisplatin (P), and Concomitant Boost Radiation for Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck (SCHN)

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 18 de mayo del 2002

Presenter: B Glisson
Presenter's Affiliation: MD Anderson Cancer Center, Texas
Type of Session: Poster

Background

• Both concurrent chemoradiation, with conventionally fractionated radiation (RT), and concomitant boost RT have been shown in randomized trials to improve the locoregional control in advanced SCHN.
• Docetaxel (D) has been shown to have radiosentizing properties in vitro and clinical activity when given as a single agent in SCHN. When given weekly with concurrent radiation, previous studies suggest a maximum tolerated dose of 25 mg/m2.
• Cisplatin is also a known radiosensitizing agent with proven activity in SCHN.
• Pre-clincal data suggest a supra-additive effect of taxane/platinum combinations.
• This study incorporates the taxane/platinum combination of docetaxel/cisplatin (D/C)into concomitant boost RT, with the objectives of identifying the maximum tolerated dose of D/C when given in two different dosing schedules, as well as the acute and late toxicities and the efficacies of these two schedules.

Materials and Methods

• Arm 1 of this study involved initial dose levels (dose level 0) of 15 mg/m2 docetaxel and 20 mg/m2 cisplatin, given every week for the first 4 weeks of RT.
• In Arm 2, dose level 0 consisted of 40 mg/m2 of docetaxel and 60 mg/m2 of cisplatin, given in week 1 and week 4 only of RT.
• RT was 1.8 Gy/day, 5d/week, weeks 1-4, with 1.8 Gy q am and 1.5 Gy q pm to a smaller field beginning week 4. The total dose was 72 Gy given over 6 weeks.
• Twenty patients were entered in this study; 14 in Arm 1 and 6 in Arm 2.

Results

• With a median follow-up of 21 months, 19 patients are evaluable; one patient died 5 weeks after treatment at an outside facility of cardiorespiratory arrest following the de-cannulation of his tracheostomy.
• In Arm 1: - 7 of 14 evaluable patients developed Grade 4 mucositis - 7 developed Grace 3 skin toxicity - 4 patients had prolonged mucositis, defined as no improvement in swallowing function at 6 weeks post-treatment - 11 patients had a complete response (CR) at the primary site - 8 patients had a CR at involved nodal sites, for a total of 8 patients with a CR at both sites - 6 patients had partial responses (PR)
• In Arm 2: - 2 of 5 evaluable patients developed Grade 4 mucositis - 5 developed Grade 3 skin toxicity - 3 patients had prolonged mucositis - 1 patient died in the immediate post-treatment period - 3 patients had a CR at both the primary and nodal sites - 2 patients had a PR
• At 6 weeks post-treatment, 12/19 patients remained dependent on a feeding tube, and 1 patient remained tracheostomy-dependent.
• With 1 one year of follow-up, 6 of 16 evaluable patients remained feeding tube-dependent, and 2 patients were dependent on a tracheostomy.
• 3 patients recurred locally, 2 recurred regionally, and 1 had distant metastases

Author's Conclusions

• With the weekly dosing schedule used in Arm 1, the authors conclude that dose level 0 is at or near the maximum tolerated dose (MTD).
• With the Arm 2 dosing schedule (weeks 1 and 4 only), dose level 0 is above the MTD.
• A Docetaxel/Cisplatin combination with synchronous, concomitant boost radiation is feasible with aggressive supportive care.
• Arm 1 is being further evaluated in Phase II trial.
• The Arm 2 dosing schedule will be evaluated with reduced doses of this chemotherapy combination.

Clinical/Scientific Implications

Advanced SCHN remains a clinical challenge, despite the recent advances of concurrent chemoradiation and concomitant boost radiation as separate therapies. The fusion of these two regimens has been shown to be feasible in this and other Phase I trials. This study is the first to use the combination of docetaxel/cisplatin in this manner. Further trials, including the ongoing phase II study of D/C by these authors, are indicated. The comparable efficacy of combining chemoradiation with an altered radiation schedule, versus either of these modalities only, can only be determined by a phase III, randomized study.

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