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Twenty-two patients with recurrent small-cell lung cancer (SCLC) were treated with single-agent etoposide 50 mg/m2/d by mouth for 21 consecutive days. Eleven patients had received previous chemotherapy with cyclophosphamide, doxorubicin, and vincristine (CAV) or etoposide (CAE) or both (CAVE). Four of the latter patients also received salvage treatment with cisplatin and etoposide (EP). Nine patients had been treated with EP as induction therapy, while two patients had received high-dose cyclophosphamide, etoposide and cisplatin (HDCEP). Altogether, 18 patients had received previous intravenous etoposide. The median time off chemotherapy was 4.5 months (range, 1 to 28.9 months). Ten patients (45.5%; 95% confidence interval [CI], 27% to 65%) achieved a complete or partial response. Responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide. Median response duration was 4 months (range, 1.5 to 9.5 months) and median survival was 3.5+ months (range, 1.0 to 15+ months). Leukocyte and platelet nadirs were 1,800/microL and 160,000/microL, respectively, during cycle 1 of treatment and occurred between days 21 and 28. Overall, total leukocyte count decreased to less than 1,000/microL during 10 of 56 cycles (18%). Five patients required six hospitalizations for neutropenia and fever. There were two toxic deaths due to sepsis. Platelet counts less than 50,000/microL occurred in 14 cycles (25%). Alopecia developed in all patients; gastrointestinal toxicity was uncommon. This schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with SCLC.
Osteoblastomas of the cervical spine frequently occur with anterior vertebral body involvement despite the classical teaching, which suggests that involvement is usually confined to the posterior elements. A review of osteoblastomas that involved the cervical spine was conducted at a single institution over 20 years. Four patients were identified with osteoblastoma of the cervical spine from a total of 13 spinal osteoblastomas, and their conditions were assessed to determine the anatomic extent of neoplastic involvement, the surgical margins obtained at resection, methods of spinal stabilization, and local recurrence rate. A mean follow-up time of 11.4 years was obtained. Posterior surgical extirpation of the neoplasm can successfully be accomplished with good long-term results by achieving intralesional margins. Patients with cervical spine osteoblastomas represent a separate subset from patients with other spinal osteoblastomas because of their unique appearances.
The efficacy of the addition of prednisolone to tamoxifen as adjuvants to mastectomy in patients with primary breast cancer who were at a high risk of recurrence was investigated in a randomized trial. Primary carcinomas were collected from a series of 169 patients with loco-regional disease, undergoing mastectomy. The activities of alpha-glycerolphosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the carcinomas were estimated biochemically and the ratio of the two enzymes was used to as the parameter to determine the risk of recurrence. 116 patients with a high risk of recurrence within five years of mastectomy were then randomized to either tamoxifen (2x20 mg/day) or tamoxifen+prednisolone (3x2.5 mg/per day) until recurrence. The patients are currently followed quarterly. The data were analysed at a median follow-up of 26 months (range 7-62 months). The probabilities of both disease-free and overall survival were not significantly different in either arm of the trial, indicating that there is no advantage in combining prednisolone with the antioestrogen. Recently, similar findings in terms of response have been reported for patients with metastatic disease treated with the same combination, raising doubts over the role of prednisolone in the management of patients with endocrine treatments.
To evaluate surgical results of resection of second (recurrent) pulmonary metastases from adult soft tissue sarcoma, the survival of 39 patients was analyzed retrospectively. With the exclusion of two patients (one with interval metastases between staged resections and one without histologically proved metastases), three patients were found to have unresectable disease (median survival, 7 months). A significantly (P = 0.0001) longer median survival (28 months) was found for 34 patients whose recurrent metastases were completely resected. The only other factor predicting significantly longer post-thoracotomy survival was resection of a solitary metastatic nodule (median survival, 65 months). Patients who had two or more recurrent nodules resected had a median survival of 14 months only (P = 0.01). Although trends toward longer survival were noted for other prognostic factors, none reached statistical significance. We conclude that the complete resection of a solitary second (recurrent) pulmonary metastatic nodule from adult soft tissue sarcoma predicts long-term survival.
Between 1979 and 1988, 26 patients with pulmonary metastases from adult soft-tissue sarcomas were treated with Adriamycin (doxorubicin hydrochloride), Cytoxan (cyclophosphamide), and DTIC before metastasectomy. Thirty-eight thoracotomies were performed with postoperative complications in 5 patients (5/38, 13.2%) and one postoperative death (1/38, 2.6%). Two patients had benign lesions at thoracotomy and were excluded from further survival analysis. The median survival of the remaining 24 patients after thoracotomy was 18.5 +/- 5.9 months, and the actuarial 5-year survival was 22%. Five patients (5/24, 21%) achieved a clinically complete response with preoperative chemotherapy, but all had recurrence in the lung and underwent resection of pulmonary metastases. Seven patients (7/24, 29%) achieved a partial response and had residual disease resected at thoracotomy. Twelve patients (12/24, 50%) showed either no change or disease progression while receiving chemotherapy and were referred for resection. Postthoracotomy disease-free survival and postthoracotomy overall survival did not differ significantly between the three groups. One patient in the group showing no change or progression of disease while receiving chemotherapy is alive without recurrence 57 months after initial pulmonary metastasectomy. Chemotherapy can be used for the initial treatment of pulmonary metastases from adult soft-tissue sarcomas. However, survival after resection of pulmonary metastases cannot be accurately predicted based on the clinical response to preoperative chemotherapy.
The value of resecting pulmonary metastases from malignant melanoma was retrospectively examined. Between 1981 and 1989, 56 patients (35 men and 21 women with a mean age of 49 years) had 65 pulmonary resections for histologically proven metastatic melanoma after treatment of the primary tumor. In patients undergoing thoracotomy, 50% (28/56) had pulmonary metastases as the initial site of recurrence. Twenty-eight patients (50%) had local-regional recurrence before the development of lung metastases. Eight lobectomies, two segmentectomies, and 55 wedge excisions were done. Fifty-four patients (54/56, 96%) underwent complete resection, and there were no operative deaths. The postthoracotomy actuarial survival was 25% at 5 years (median interval, 18 months). Location of the primary tumor, histology, thickness, Clark level, local-regional lymph node metastases, or type of resection was not associated with improved survival. Patients without regional nodal metastases before thoracotomy had a median survival of 30 months compared with 16 months for all others (p = 0.04). Patients with lung as the site of first recurrence had a median survival of 30 months compared with 17 months for patients with initial local-regional recurrence (p = 0.038, log-rank test). Despite systemic spread, patients with isolated pulmonary metastases from melanoma may benefit from metastasectomy.
Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.
Between November 1988 and March 1990, 24 patients with endobronchial tumors that had recurred after external beam radiation therapy were treated with high dose rate intraluminal irradiation. A remote afterloading high dose rate unit was used, and most patients received two endobronchial treatments, separated by a two week interval. All patients were given the same dose and dose specification to assess the feasibility and complications of the therapy. At each treatment, 15 Gy were delivered with dose specified at a radius of 6 mm from the center of the source, which corresponds to a dose of 9 Gy at a radius of 1 cm. Overall, 21 of 24 patients (88%) showed good symptomatic improvement. Of 18 patients whose chest x-ray showed evidence of collapse or atelectasis caused by tumor obstruction, 15 (83%) had evidence of reaeration. The median duration of palliation, marked by symptoms or a chest x-ray that worsened, was 26 weeks, the range varying from seven to 40 weeks. No patient died as a result of therapy and only one had a complication, bronchospasm, which responded well to bronchodilators. One patient died of hemoptysis approximately three months after treatment. Five additional patients, who were treated off protocol because they had an Eastern Cooperative Oncology Group performance status of greater than two, also received endobronchial irradiation. All five died within one month from worsening pulmonary disease, and we do not recommend endobronchial irradiation for patients with an Eastern Cooperative Oncology Group performance status of greater than two. We conclude that high dose rate endobronchial brachytherapy effectively relieves the symptoms of endobronchial obstruction due to recurrent lung cancer and can be given safely as an outpatient procedure. As the complications were minimal in this series treated with a uniform dose of 15 Gy per treatment, future studies should aim at determining the maximum tolerated dose. This technique may also be helpful as a boost after maximal external beam irradiation or to open up areas of atelectasis prior to external beam irradiation.
From April 1989 to August 1990, 17 patients with Stage 3 or 4 epithelial ovarian cancer (EOC) were treated with intravenous carboplatin (160-400 mg/m2) for refractory or recurrent disease after first-line treatment with cisplatin-based combination chemotherapy. Of fifteen patients evaluable for activity, two complete responses and two partial responses were seen, for a response rate of 27%. The duration of response was 4.5, 5, 8, and 9.2 months, respectively, and responders survived longer than nonresponders. Of the nine evaluable patients receiving carboplatin as the first salvage treatment, four responses were seen. Dose selection for the first cycle of carboplatin was based on previous treatment, and adjustments were made on the basis of myelosuppression. In general, treatment was well tolerated--severe myelosuppression occurred after 6 of 73 cycles. This review confirms previous reports of anti-tumor activity of carboplatin in patients with refractory or recurrent advanced EOC who respond to first-line treatment with cisplatin. Further evaluation may help define the toxicity and efficacy of salvage treatment with carboplatin compared to cisplatin in patients who recur after a prolonged disease-free interval after first-line cisplatin-based therapy.