Cisplatin as a radiation sensitizer in the treatment of advanced head and neck cancers. Results of a phase II study.
BACKGROUND
Surgery and radiotherapy mainstays in the management of advanced head and neck cancer, although historically, only 20-30% of patients survive. Therefore, in an attempt to improve locoregional control and survival, a multimodal protocol using cisplatin as a radiosensitizer was implemented.


METHODS
Between 1984 and 1990, 68 patients with advanced head and neck cancer (Stages III and IV) were treated with a regimen consisting of an induction phase of 4500 cGy and two cycles of cisplatin followed by an eradicative phase of either radical surgery (Group A, 27 patients) or radical radiotherapy (Group B, 41 patients). The maintenance phase chemotherapy consisted of adjuvant 5-fluorouracil (5-FU) and cisplatin after completion of locoregional treatment. Of the 68 patients, 19 had Stage III disease, and 49 had Stage IV; 21 had no regional lymph node metastases (N0), and 47 had regional lymph node metastases (N+).


RESULTS
The induction phase yielded a 26% (18 patients) complete response (CR) rate and a 57% (39 patients) partial response (PR) rate (response > 50%), yielding an overall response rate of 83%. Eleven patients (16%) had stable disease (ST) (i.e., < 50% response). The 2-year survival rates by initial treatment response for patients who had a CR, a PR, and stable disease were 53%, 56%, and 36%, respectively; for Groups A and B, 63% and 45%, respectively; for Stages III and IV, 68% and 43%, respectively; and for N0 and N+, 69% and 43%, respectively. In Group A, 14 of 27 patients (52%) had no viable tumor in the surgical specimen (i.e. had pathologic complete tumor clearance [CTC]); this subgroup had a 5-year survival rate of 58%. Ten patients (37%) who had gross total resection of tumor with negative margins but had tumor present in the specimen had a 5-year survival of 22%. In Group B, the 5-year survival rate was 43% for 27 patients who achieved CR after completion of radical radiotherapy (total tumor dose, 6480-7020 cGy). The 5-year survival rate of the 14 patients who had a PR and stable disease after radical radiotherapy and 3 patients whose resection was incomplete was 0%. The overall 2- and 5-year survival rates for all patients were 53% and 32%, respectively. Of 21 patients in whom treatment failed, most (90%) had a locoregional recurrence: 13 local recurrences (62%), 5 regional (24%), and 1 locoregional (5%). Two patients (10%) experienced failure at distant sites (the lung). Major treatment-related morbidity developed in two patients.


CONCLUSIONS
Although induction chemotherapy-radiotherapy produces a high clinical response rate, this does not translate into improved survival compared with historical controls. A subgroup that showed complete tumor clearance (CTC or pathologic complete response) at surgery had an apparent improved survival and merits further study. Patient selection did not appear to be a factor for the CTC group, because the majority of patients in this group had partial responses to induction therapy, nodal disease and advanced tumor stage, and tumor presence in unfavorable sites.
Chougule
P B
PB
Department of Radiation Oncology, Rhode Island Hospital, Providence 02903.
Suk
S
S
Chu
Q D
QD
Leone
L
L
Nigri
P T
PT
McRae
R
R
Lekas
M
M
Barone
A
A
Bhat
D
D
Bellino
J
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012074:Remission Induction; D016019:Survival Analysis; D017211:Treatment Failure
D011838:Radiation-Sensitizing Agents; D002945:Cisplatin