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Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer

Phase 2
18 Years
Not Enrolling
Squamous Cell Carcinoma

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Trial Information

Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer

Cancers of the head and neck (H&N) comprise 5% of all cancers, with 40,000 new cases
diagnosed annually. Surgery followed by irradiation or irradiation alone has been the
standard of care for locally advanced Stage III and IV patients. With this approach, fewer
than 30% of patients achieve long-term remission, and most recur locoregionally.
Neoadjuvant chemotherapy has been administered prior to definitive therapy with response
rates ranging from 60-90%; with pathologic CR rates documented in 30-70% of clinical
responders. However, large randomized trials have shown no improvement in overall survival.

Because induction chemotherapy alone does not appear to improve long-term disease free
survival in advanced head and neck cancers, concomitant chemotherapy and radiation has been
pursued in patients with locally advanced head and neck cancers. Improved disease-free
survival has been demonstrated with a variety of agents. The concept of synergy between
radiation and chemotherapy is well established in vitro. Various schedules of radiation and
chemotherapy have been utilized including weekly chemotherapy during radiation, chemotherapy
given every three weeks during hyperfractionated radiation and alternating chemotherapy and

One exciting new chemotherapeutic agent, Paclitaxel has been shown to radiosensitize cancer
cell lines in vitro. Recent studies have added Carboplatin to Paclitaxel in tandem or
concurrently with radiation in hopes of improving response rates. From in-vitro data, it
appears that the optimum schedule for the combination of Paclitaxel and radiation is to
first induce G2/M arrest with Paclitaxel and follow this with radiation therapy. In a
recent study by Chendil, et al, a novel radiation scheme appeared to enhance the response of
both p53 wild type and p53 mutant cancer cell lines to chemotherapy. In vitro data with
Carboplatin also indicates an additive effect when given prior to irradiation using various
cell lines. What has not been evaluated, is whether a neoadjuvant regimen of Paclitaxel and
Carboplatin followed by 4 small fractions of radiation can be given safely and effect an
improved response rate in patients with bulky T2, Stage III and IV H&N cancer. We propose
the use of two cycles of Paclitaxel and Carboplatin followed by four small fractions of
radiation, prior to definitive treatment (surgery or radiation). It is hoped that using
radiation as a chemoenhancer will increase the response rate to induction therapy in this
population of patients.

Inclusion Criteria:

1. Adult patients greater than 18 years of age.

2. ECOG performance status of 0, 1 or 2.

3. Patients with pathologically documented bulky T2, III and IV squamous cell cancer of
the head and neck (excluding M1 disease), within 2 months of diagnosis. Bulky T2
tumors are defined as those that have a volume of disease greater than 35 cm3 as
measured by CT or MRI scan (26).

4. Patients will be medically fit for undergoing chemotherapy. Specifically:

1. no evidence of active angina pectoris or ventricular arrhythmias; no myocardial
infarction within the last six months. (Patients with medically controlled
hypertension or congestive heart failure are eligible.)

2. an absolute neutrophil count of > 1000/uL and platelet count > 100,000/uL

3. serum total bilirubin < 1.5 mg/dL

4. Creatinine Clearance greater than 50 ml/min

Using an actual or calculated creatinine clearance using the formula:

(140 - age) x (wgt in kg)*/(serum creatinine)x(72)*= multiply by 0.85 for

5. if a pre-existing grade I neuropathy exists, patients must be willing to risk
worsening neuropathy secondary to Paclitaxel. Patients with grade II or greater
neuropathy will be excluded from study.

6. ability to give written, informed consent to participate in the trial.

5. Patients will have measurable disease as determined by MRI or CT scan or evaluable
disease determined by panendoscopy to be eligible for enrollment on this study.

Exclusion Criteria:

1. Pregnant females. Males and women of childbearing potential must use effective
contraception in order to prevent pregnancy during therapy.

2. Patients with a history of previous or current malignancy at other sites diagnosed
within the last 5 years, with the exception of adequately treated carcinoma in-situ
of the cervix or basal or squamous cell carcinoma of the skin. Patients with a
history of other malignancies, who remain free of recurrence or metastases for
greater than five years are eligible.

3. Patients with active infection will not be eligible for this protocol until the
infection is treated and the symptoms have clinically resolved.

4. Patients with a history of allergy to drugs utilizing Cremophor in the formulation.

5. Prior induction chemotherapy, prior irradiation or surgery will not be allowed.

6. Patients with metastatic disease will not be eligible for this study.

7. Patients with grade II or greater peripheral neuropathy will be excluded from study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate to induction chemotherapy prior to definitive therapy (surgery or radiation)

Outcome Time Frame:

assessed pre-study and once between days 36-57

Safety Issue:


Principal Investigator

Susanne Arnold, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kentucky


United States: Institutional Review Board

Study ID:




Start Date:

May 2000

Completion Date:

October 2012

Related Keywords:

  • Squamous Cell Carcinoma
  • head and neck
  • squamous cell carcinoma
  • squamous cell
  • carcinoma
  • paclitaxel
  • carboplatin
  • radiotherapy
  • induction therapy
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms