Release: July 29, 2000
Contact: Kenneth Satterfield
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In San Francisco (7/28-8/2)
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CHEMOTHERAPY FOLLOWED BY SURGERY IS NO MORE EFFECTIVE THAN SURGERY ALONE AS A TREATMENT FOR ORAL CAVITY CANCER
San Francisco, CA -- The results of a randomized trial conducted by a team of Italian head and neck surgeons indicate that a combined chemo-surgical approach for the treatment of oral cavity cancer does not offer an increased chance of survival, when compared to surgery alone in advanced oral cavity cancer. Accordingly, they recommend the standard care for advanced operable oral cavity cancer should be surgery followed by radiation in high risk patients.
The authors of the study, "Surgery Versus Primary Chemotherapy and Surgery in Cancer of the Oral Cavity: Preliminary Report of Final Results of a Randomized Study," are C Grandi MD, L Licitra MD, R Cavina MD, M Guzzo MD, L Mariani PhD, S. Lovullo, G. Cantu MD, G Bonadonna MD, R Molinari MD, all from the Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy. The findings were presented before the 5th International Conference on Head and Neck Cancer, being held July 29 through August 2, at the San Francisco Marriott, San Francisco, CA. More than 1,500 leading head and neck surgeons from the United States and 46 nations will gather to hear the latest medical research in the diagnosis, treatment, and reconstruction associated with head and neck cancer. The medical conference is sponsored by the American Head and Neck Society, www.headandneckcancer.org.
Methodology: A multi centric randomized trial comparing primary chemotherapy followed by surgery (arm A) against surgical standard treatment (arm B) in patients with an oral cavity cancer was activated at the National Cancer Institute, Milan, Italy, in 1989. Patient accrual was closed in December 1999.
All patients with operable oral squamous cancer staged T2-4 NO-2 MO were enrolled, stratified by institution and nodal stage. Chemotherapy was cisplatin 100 mg/m2, day one, and 5FU 1000 mg/m2 120h for three cycles. At the end of the study, after exclusion of two patients who refused any treatment, 195 patients were included, 98 patients in arm A , 97 in arm B. The mean age was 55; a male/female ratio was 165/32.
The study design was characterized by: Phase III multi centric trial with an Estimated five-yr DFS (differential for survival) of a control arm: 50 percent: estimated five DFS differences, 20 percent.
The planned study duration was five to six years; the requested number of patients was 258. The trial was carried out in a single center (INT Milan), so that the accrual was much lower than expected, and finally the study had to be closed without reaching the planned number of patients.
Results: The distribution of patients by stage grouping in the arms A and B respectively was as follows: II: 25%-25%, III: 47%-41%, IV: 28%-34%.
Chemotherapy was stopped in 27 cases, due to lack of response (11 patients), refusal (3), toxicity (12), protocol violation (one) and was completed at reduced doses in eight patients. Three toxic deaths were recorded, due to sepsis in neutropenia (one) and cardiac failure (two). Grade III-IV (WHO) were registered as follows: cardiac (six), hematological (27), vomiting (seven), Stomatitis (eight), hemorrhage (one). Three patients in the chemotherapy "arm" did not have surgery; two for drug toxicity, and one for refusal. No surgical death occurred and surgical morbidity was similar in both arms.
An objective clinical response rate to chemotherapy was 76 percent, with a complete remission rate of 27 percent. No or minimal residual disease was found in 33 percent of the cases who had at least two cycles of chemotherapy. Histologically positive margins were detected in 12 percent of the cases in arm B vs. four percent in arm A.
At June 30, 2000, the number of patients dead from cancer recurrence in arm A and B was 31 and 32 respectively. Seven patients in arm A and 12 patients arm B died of a second primary tumor. The five-year overall and DFS survival rate of the whole group was 55 percent (95 percent C.I.: 48-62 percent) and 60 percent (95 percent C.I.: 54-66 percent) respectively. No significant difference in five year overall and DFS survival (at a five percent level) was found between the two treatment arms; 56 percent and 53 percent (95 percent C.I.: 43-63 percent) in arm A and B respectively. Postoperative radiotherapy was needed in 46 percent of patients in arm B versus 33 percent in arm A. In a chemotherapy arm, patients achieving a complete response after chemotherapy had a very favorable prognosis: 87 percent 5-year DFS.
Conclusions: The research team concluded from the study results:
-- There is no significant advantage in terms of survival of a combined chemo-surgical approach when compared to surgery alone in advanced oral cavity cancer.
-- Standard care of advanced operable oral cavity cancer should be surgery followed by radiation in high risk patients.
-- Subset analysis of patients achieving a clinical or pathological complete response indicated that chemotherapy is able to identify a subgroup of patients with a very favorable prognosis.
-- The evaluation of other prognostic and/or predictive factors (cell Kinetics, p53, bcl2, HPV) is still ongoing.
-- Treatment individualization according to response to chemotherapy and possibly other prognostic factors may guide the design of further trials.
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