Objectives: To determine outcomes in local-regional control and overall survival in patients with squamous locally advanced cancer of the oral cavity, based on intention-to-treat with neoadjuvant chemotherapy followed by surgery or radiation therapy. Methods: Two hundred and four out of 1,089 patients analyzed met the defined criteria. All had squamous cell carcinomas of the oral cavity in stage III or in nonmetastatic stage IV and were selected for surgery or radiation therapy (if located in the tonsils or in the base of the tongue). Chemotherapy was based on cisplatin 120 mg/m² i.v. day 1 plus bleomycin 20 mg/m² days 1–5 in continuous i.v. perfusion or plus 5-fluorouracil 1,000 mg/m² days 1–5 in continuous i.v. perfusion. A total of 418 cycles were given to 204 patients (mean 2.049 per patient). Definitive surgery (n = 73; plus adjuvant radiation therapy) or definitive radiation therapy (n = 131) was performed. Results: One hundred thirty-five out of 204 (66%) patients were chemotherapy responders, 16% complete and 50% partial. One hundred ninety-four patients (95%) completed 2 courses of chemotherapy. After neoadjuvant chemotherapy, 34 out of 46 patients considered inoperable initially (74%) obtained a disease-free status with surgery. Eighty-three percent of surgical patients obtained a disease-free status (initial tumor control) versus 72% of radiation therapy patients. Disease-free survival rates at 5 years were 26 and 22%, respectively. A better prognosis was observed in stage III over IV (p = 0.02); primary tumor in the retromolar trigone, palate or buccal mucosa over tongue, tonsil or floor of the mouth (p = 0.0085); negative cervical nodes over positive (p = 0.0186); responders to chemotherapy over nonresponders (p = 0.0003); and adjuvant postsurgical radiation therapy (p = 0.0013). Causes of death were relapses in local area (86%), regional nodes (10.5%) or distant metastases (3.5%). Eleven patients (5%) died of a second primary. The main toxic effects were vomiting in 9% of patients and hemolytic-uremic syndrome in 3% of the patients treated with bleomycin. Conclusions: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. In this study, patients have an acceptable long-term survival.

Vertebral Artery Occlusion After ChemotherapyTo the Editor:We have read the interesting report by Periard et al about cisplatin-induced strokes. 1 The role of tumors as risk factors for vascular disorders has long been established. However, there is little evidence regarding the effects of chemotherapy. Several reports describe vascular toxicity in young patients treated with cisplatin, and these studies suggest a casual link. 2,3 We present a patient who experienced a stroke due to vertebral artery occlusion after chemotherapy.A 48-year-old female patient was admitted to our hospital with nausea, vomiting, and headache. The patient also complained of tingling in the left side of her face. She had previous history of ovarian thecoma that was treated surgically on 3 occasions because of relapse and was finally treated with chemotherapy. The first dose of cisplatin, etoposide, and bleomycin was given 4 days before admission.On admission she presented with Horner syndrome, facial asymmetry, impaired elevation of the left soft palate and dysfonia. She also had dismetria in left arm. Her gait deviated to the left side.Blood tests were unremarkable, except for low leukocyte levels, with low neutrophyle level, which was related to the side effects of chemotherapy, as levels returned to normal in posterior tests without specific treatment. The MRI showed brain damage in the left occipital region, left cerebellum hemisphere, and left thalamus compatible with acute ischemic stroke in the vertebralbasilar territory. MRI angiography showed obstructed flow in the left vertebral artery with no other abnormalities. Thrombophiliaautoimmunity screening, syphilis, and HIV tests, ECG, echocardiogram, cerebral spinal fluid, and chest x-ray were unremarkable. The patient treated with clopidogrel recovered properly in the following days. Therefore, we report the case of a patient with an ischemic stroke just after the first course of chemotherapy. She did not have other risk factors for cerebrovascular disease. Vascular events have been described as a rare complication in relation to anticancer drugs. 4 Specifically, some authors have reported events in relation to cisplatin, [1][2][3][5][6][7] as well as to the combination of cisplatin, etoposide, and bleomycin. 2,5,6 We have not found any other case in literature of occlusion of a big cerebral artery induced by chemotherapy. Cases of aortic and other peripheral artery occlusion have been described. 3,4,6 As for brain arteries, only cases of carotid branch thrombosis have been found. 2,7 The case reported here would be the first one related to a vertebral artery.The mechanisms of such vascular events are probably multifactorial (endovascular damage, platelet aggregation, vasospasm or abnormalities in the coagulation cascade directly produced or induced by chemotherapy). [1][2][3][5][6][7] In agreement with all the referred authors, it is concluded that once a vascular event has occurred, discontinuation of cisplatinbased chemotherapy is mandatory.

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