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A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.

One hundred thirty consecutive patients with metastatic spinal cord compression (MSCC) were entered in a therapeutic protocol in which radiation therapy (RT) played the main role. When MSCC is diagnosed by clinical-radiologic methods such as myelography with or without computed tomography (CT) or magnetic resonance imaging (MRI), steroids are given and RT treatment started within 24 hours. When diagnostic doubts exist or stabilization is necessary, surgery precedes RT. Chemohormonal potentially responsive tumors are also treated with chemotherapy or hormonal therapy. Twelve patients (9.2%) underwent surgery plus RT, and 118 (90.8%) received RT alone. Thirteen (11%) early death patients were not evaluable. The 105 evaluable cases that received RT alone were analyzed. Median follow-up was 15 months (range, 4 to 38 months). Response among patients with back pain was 80%. In cases with motor dysfunction, 48.6% improved, and in 33 of 105 patients (31.4%) without motor disability there was no deterioration. Forty percent of patients with autonomic dysfunction responded to RT. Median survival time was 7 months with a 36% probability of survival for 1 year. The median duration of improvement was 8 months. The most important prognostic factor was early diagnosis. Radiosensitivity of tumor was only important in paraparetic patients in predicting response to RT. Complete myelographic block significantly diminished response to RT. Vertebral collapse did not influence response or survival.

Fifty-six breast cancer patients with metastatic spinal cord compression were consecutively treated with radiation therapy alone. All patients received steroids plus chemotherapy and/or hormonal therapy. Emergency radiation therapy was administered using a split-course regimen: 5 Gy for 3 days, stopped for 4 days and, only in responders, a further 3 Gy for 5 days (time dose fractionation 68). Median follow-up was 22 months (range, 4 to 52 months). Response and survival were assessed on the basis of, pretreatment and posttreatment walking capacity, presence of vertebral body collapse or osteolysis, presence of other metastatic sites apart from bone and chemotherapy and/or hormonal therapy. In 89% of patients with back pain the pain disappeared or lessened. Four of 6 cases (67%) with urinary dysfunction responded to radiation therapy. Of 35 cases with motor dysfunction at the time of diagnosis, 21 (60%) regained the ability to walk and another five (14%) who were able to walk with support at diagnosis did not deteriorate. All 21 cases without motor deficits before treatment maintained good motor performance after radiation therapy. Response to therapy was better in pretreatment walking than in nonwalking patients (97% vs 69%; p less than 0.02). Probability of duration of response at 1 year was 59% and 10% for posttreatment walking and nonwalking patients, respectively (p less than 0.0001). One year survival probability was 66% for posttreatment walking and 10% for posttreatment nonwalking patients, respectively (p less than 0.0001). Pretreatment and posttreatment ambulatory status were the most important prognostic factors.

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

Twenty patients suffering from malignant hemopathies (mean age 31.7 years) were given hyperfractionated total body irradiation (TBI) (120 cGy/3 fractions per day: total dose = 1440 cGy/4 days) as conditioning for T-depleted HLA identical allogeneic bone marrow transplantation. At an average of 12 months (range of 4.5-22 months) follow-up there were two cases of early death and two cases (11%) of rejection. There were no cases of acute or chronic graft versus host disease (GVHD) nor cases of interstitial pneumonitis. The average time for durable engraftment was 22 days. Disease-free survival at 12 months was 65%. To improve the results and further reduce the percent of rejection, the authors propose intensifying the immunosuppressive conditioning by increasing the cyclophosphamide dose and that of TBI so that a total dose of 1560 cGy is reached.

A non-randomized prospective trial in which radiotherapy (RT) alone played the major role in the treatment of metastatic spinal cord compression (MSCC) is reported. Diagnosis was formulated on myelography and/or myelography plus computed thomography (CT). Of 51 cases treated, 48 are evaluable. The therapy consisted of radiation alone (42 cases) or decompressive laminectomy followed by radiotherapy (6 cases). Surgery was performed when the site of the primary tumor was unknown. The group of patients who received radiotherapy alone (42 of 48 evaluable cases) are analysed in this report. Medium to high doses of steroids were administered to all patients depending on the gravity of the case. Patients with chemo- or hormone-responsive primary tumors also received chemotherapy and/or hormone therapy. Pain relief, assessed by comparing use of narcotics and minor analgesics before and after treatment, was achieved in 54% cases (confidence limits, CL = 38-69%). In 36% (CL = 22-51%) of patients back pain diminished to the point when only milder analgesics were necessary (partial remission). Motor performance, based on patients' ability to walk, improved in 48% cases (CL = 31-65%). The 19 patients who were ambulatory before RT, did not deteriorate after treatment. Sphincter function, evaluated by patient's need for indwelling catheter, improved in 3 of 7 automatic dysfunction cases. It was found that early diagnosis was more important than primary tumor type for predicting a good was found that early diagnosis was more important than primary tumor type for predicting a good prognosis. In fact, all ambulating patients responded to treatment independent of the radiosensitivity of the tumor histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Surgery is the primary treatment for patients with stage I, II, or IIIA non-small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established. Methods: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m 2 on day 1), vindesine (3 mg/m 2 on days 1 and 8), and cisplatin (100 mg/m 2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided. Results: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P = .589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P = .128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival. Conclusion: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.