Adjuvant Chemoradiation With Weekly Oxaliplatin in Resected Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: Oxaliplatin; Radiation
Intervention description: 70mg/m2 IV over 120 min once a week during radiation; 200 cGy/day - Megavoltage equipment with energy of Cobalt 60 or higher - Daily from Monday to Friday
Intervention MeSH terms: Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; oxaliplatin; resected squamous cell carcinoma; Eloxatin™

Summary:

      Oxaliplatin-containing regimens have been safely and successfully used in combination with
      concurrent radiation in treatment of solid tumors such as rectal and esophageal cancers. The
      Lyon R0-04 phase II trial utilized the combination of Oxaliplatin, infusional 5-fluorouracil
      (5-FU) and radiation in the treatment of rectal cancer. The trial showed a combined
      preoperative chemoradiotherapy and Oxaliplatin-containing regimen is well tolerated with no
      increase surgical toxicity. The good response rate observed warrants its use in further
      clinical trials.

      The combination of oxaliplatin, 5-FU, and radiation also have been used in a Phase I/II trial
      in esophageal cancer. In this particular trial, eligibility included therapeutically naïve
      esophageal cancer subjects with clinical disease stages II to IV. Initial doses and schedules
      for cycle 1 consisted of Oxaliplatin 85 mg/m2 on days 1, 15, and 29; continuous infusion of
      5-FU 180 mg/m2 for 24 hours for 35 days; and radiation therapy (RT) 1.8 Gy in 28 fractions
      starting on day 8. At completion of cycle 1, eligible subjects could undergo an operation or
      begin cycle 2 without RT. Postoperative subjects were eligible for cycle 2. Stage IV subjects
      were allowed three cycles in the absence of disease progression. 38 subjects were treated (22
      stage IV, 16 stage II-III). 38 eligible subjects received therapy: 22 non-invasively staged
      as IV and 16 non-invasively staged as IV and 16 non-invasively staged as II and III. 36
      subjects completed cycle 1, 29 subjects started cycle 2, and 24 subjects completed cycle 2.
      The combined-modality therapy was well tolerated, but dose limiting toxicity (DLT) prevented
      Oxaliplatin and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3
      and two grade 4 clinical toxicities were noted in eight subjects. After cycle 1, 29 subjects
      (81%) had no cancer in the esophageal mucosa. 13 subjects underwent an operation with intent
      to resect the esophagus and 5 subjects (38%) exhibited pathologic complete responses. There
      was no surgical mortality. Only 1 subject developed post-operative tracheoesphageal fistula.
      The results of these trials described above indicated that combination of oxaliplatin and
      radiation is safe and efficacious and dose not compromise surgical wound healing, repair and
      clinical outcome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All subjects must have histologically or cytologically confirmed diagnosis of squamous
             cell carcinoma of the head and neck region. Primary tumor sites include: oral cavity,
             pharynx (oropharynx, hypopharynx), or larynx (supraglottis, glottis subglottis).
             Nasopharynx primary will be excluded.

          -  The resected tumor must have one or more of the following high risk features:
             histologic extracapsular nodal extension involvement of ≥ 2 regional lymph nodes,
             mucosal margin of resection with invasive cancer (limited to microscopic detection
             only), tumor with perineural invasion, tumor with lymphovascular invasion, oral cavity
             and oropharynx carcinomas with positive lymph nodes metastasis at level IV or V.

          -  Radiation must begin within 28 to 56 days after surgical resection.

          -  All subjects must be 18 years of age or older.

          -  Subjects must have a Zubrod performance of 0-2.

        Exclusion Criteria:

          -  Subjects must not have distant metastatic disease (M1).

          -  Subjects must NOT have prior therapy with oxaliplatin.

          -  Subjects with any evidence of active or uncontrolled infection, recent myocardial
             infection, unstable angina, or life-threatening arrhythmia are not eligible.

          -  Patients with severe psychiatric disorder are not eligible.

          -  No other prior malignancy is allowed except for adequately treated basal cell or
             squamous cell carcinoma, in situ cervical cancer, or adequately treated Stage I and II
             cancer from which the patient is in complete remission, or any other malignancy from
             which the patient has been disease-free for 5 years.