Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.

Brain metastases are found at diagnosis in 10% of patients with small cell lung cancer. To clarify the effect of central nervous system metastases on prognosis, the records of 429 patients with small cell lung cancer were reviewed. Forty-three patients (10%) presented with brain metastases. In 18 patients the brain was the only site of metastatic disease, whereas the remaining 25 patients had at least one additional metastatic site. Forty-one of forty-three patients were treated with combination chemotherapy and cranial radiotherapy. Systemic response rates were similar for both groups. Twenty-seven patients underwent repeat central nervous system staging: 19 (70%) had a complete response, 4 (15%) a partial response, and 4 (15%) no response. Median survival of patients with only one site of metastatic disease was 11 months; patients with additional sites lived 5 months (p = 0.153). Survival in patients with only one site is similar to that in patients with limited disease (11 compared with 13 months; p = 0.074).

BACKGROUND The goal of the current study was to determine the prostate‐specific antigen (PSA) and objective response rates and the pharmacokinetics associated with a monthly × 3 one‐hour infusion of suramin in 58 patients with hormone‐refractory prostate carcinoma. METHODS A PSA response was defined as a > 50% reduction in the PSA level from baseline for at least 3 consecutive evaluations over a minimum of 6 weeks. The suramin dose was 2400 mg/m2 taken intravenously on Day 1, 1620 mg/m2 on Day 29, and 1292 mg/m2 on Day 57. All patients received 0.5 mg dexamethasone twice daily. RESULTS Among 56 evaluable patients (median entry PSA level, 229.5 ng/mL), there were 21 PSA responders (37.5%). Among 27 patients with measurable disease, there were 5 responders (4 partial and 1 complete). The median overall survival time was 15.3 months. Grade III fatigue (14.1%) was the predominant toxicity observed. Suramin plasma levels remained high even 3 months after treatment was discontinued. Among the 12 evaluable patients who previously had received chemotherapy, the PSA response rate was 42%; one response was observed among 4 patients with measurable disease, and the median survival was 12 months. CONCLUSIONS Monthly bolus suramin was well tolerated, reduced PSA levels, and induced objective responses, even in patients who previously had received chemotherapy. Cancer 2004;100:65–71. © 2003 American Cancer Society.

Three patients with widely disseminated Merkel cell tumors of the skin are presented. In all three cases, neuron-specific enolase (NSE) was demonstrated in neoplastic tissue by immunohistochemical staining, and serum NSE levels were also elevated in all three patients. Serum NSE may prove to be a useful tumor marker in this and other malignancies of neuroendocrine origin.

We evaluated thiotepa in escalating dose in a broad phase I and II study using cryopreserved autologous bone marrow transplantation to assure hematopoietic recovery. Thiotepa was administered intravenously (IV) over two hours daily for three consecutive days followed in three to four days by marrow transplantation. The daily dose ranged from 60 to 525 mg/m2 (total dose, 180 to 1,575 mg/m2). A total of 71 patients with malignant melanoma were treated. Forty-three patients (61%) had received prior cytotoxic therapy and 28 were untreated. Sixty-two patients (87%) had melanoma disseminated to at least one visceral site, nine patients had skin and/or lymphatic metastases only. As of January 1, 1988 one patient was too early to be evaluated, 15 patients were inevaluable for tumor response, four patients had a complete response (CR), and 25 patients had a partial response (PR) to treatment. The response rates (95% confidence interval) for the 55 evaluable patients and for all 71 treated patients were 53% (40% to 65%) and 41% (30% to 53%), respectively. The median duration of response was 3 months, with a range of 1 to 31 + months. Three patients were alive and well without evidence of tumor more than 1 year after treatment. Analysis of patient subsets indicated that neither total dose, previous cytotoxic therapy, or sites of metastases influenced response rate. In this study, high-dose thiotepa has demonstrated a high response rate in patients with metastatic malignant melanoma with both PRs and CRs noted. Although most of the responses were not durable, 10% of the responses lasted more than 1 year. Future studies will evaluate additional methods for increasing the response rate and improving the duration of response.