Title:                     

                    An organ-preserving selective arterial chemotherapy strategy for head and neck cancer.

                    Author:

                    Kerber CW; Wong WH; Howell SB; Hanchett K; Robbins KT

                    Address:

                    Department of Radiology, University of California at San Diego, Medical Center, 92103, USA.

                    Source:

                    AJNR Am J Neuroradiol, 1998 May, 19:5, 935-41

                    Abstract:

                      PURPOSE: Squamous cancer of the upper aerodigestive tract is a disheartening disease. Despite

                      our best efforts, the long-term survival rate remains only 15% to 40%, and surgical cures often

                      decrease the quality of life owing to the loss of swallowing and speech organs. A better

                      understanding of tumor dynamics and the discovery that thiosulfate can neutralize cisplatin led us

                      to develop a treatment plan that combines a rapid superselective high-dose intraarterial delivery of

                      cisplatin (CDDP), simultaneous intravenous infusion of its antagonist, thiosulfate, and radiation

                      therapy. METHODS: Patients with advanced head and neck squamous cancer were entered into

                      the protocol after a multidisciplinary evaluation that included CT or MR imaging. Forty-two patients

                      constituted the first cohort. After baseline angiography, an arterial acceptance test determined the

                      maximum infusion rate that the tumor's nutrient artery would accept. CDDP was then infused at

                      that rate, usually within 3 to 5 minutes, while the antagonist thiosulfate was given intravenously. In

                      the second cohort of 85 patients with stage 3 or 4 previously untreated and unresectable disease,

                      local radiation was added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was

                      delivered regionally on the basis of the known radiosensitizing effect of CDDP. RESULTS: Cohort

                      1 allowed us to develop the infusion technique and to establish a dose quantity and delivery

                      frequency. When 150 mg/m2 was administered weekly for 4 weeks, no severe toxicity was found.

                      In cohort 2, 72 (92%) of the remaining 78 patients had complete disappearance of their tumor.

                      Seventeen severe toxic events were associated with 323 femoral catheterizations. One patient

                      died of pulmonary embolus, precluding follow-up evaluation. Six patients had neurologic sequelae,

                      three with transient and three with permanent strokes. CONCLUSION: Rapid superselective

                      chemotherapy with CDDP combined with a circulatory systemic antagonist allowed delivery of an

                      antitumoral drug directly into the lesion while protecting the kidneys and bone marrow from the

                      agent's systemic effects. Use of a dose regimen of 150 mg CDDP/m2 per week for 4 weeks

                      resulted in the disappearance of a large percentage of advanced squamous cancers.

                    Language of Publication

                      English

                    Unique Identifier

                      98273572

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                    MeSH Heading (Major)

                      Antineoplastic Agents|*AD/AI/TU; Cisplatin|*AD/AI/TU; Head and Neck Neoplasms|DI/*DT/*RT;

                      Radiation-Sensitizing Agents|*AD/AE/TU; Thiosulfates|*AD/AE/TU

           MeSH Heading

                      Cerebral Angiography; Cohort Studies; Combined Modality Therapy; Dose-Response Relationship,

                      Drug; Human; Infusions, Intra-Arterial; Infusions, Intravenous; Magnetic Resonance Imaging; Time

                      Factors; Tomography, X-Ray Computed

                 Publication Type

                      CLINICAL TRIAL; CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE

                 ISSN

                      0195-6108

                 Country of Publication

                      UNITED STATES