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Biomedical subjects

J Aisner

Publications and source records attributed to J Aisner.

At least 163 records · Page 9Linked to original sources

Cyclophosphamide plasma and cerebrospinal fluid kinetics with and without dimethyl sulfoxide.

Ten patients with brain tumors and indwelling ventricular reservoirs were pretreated with 5% to 10% dimethyl sulfoxide (DMSO) (intravenous, oral, or both) and were then treated with 1.0 to 1.25 gm/m2 cyclophosphamide (CYC). All patients were also on anticonvulsants and dexamethasone. CYC and alkylating activity (alk act) in plasma and concomitant ventricular cerebrospinal fluid (CSF) were measured by gas chromatography and p-nitrobenzyl pyridine assay. CYC entered the CSF without difficulty and was lost from CSF more slowly than from plasma. Alk act did not enter CSF as well as did CYC. DMSO did not alter any measured aspect of CYC or alk act disposition. Specifically, it did not alter the CYC plasma half-life (t1/2), CSF t1/2, peak CSF: peak plasma CYC concentration ratio, or the urinary excretion of CYC. DMSO did not alter the plasma t1/2 or urinary excretion of alk act or the peak CSF:peak plasma concentration ratio of alk act. Our data show reduced plasma t1/2 of CYC and increased plasma and urinary alk act. This may reflect tht effect of long-term therapy with anticonvulsants or steroids.

Adult↗

A phase II trial of m-AMSA in the treatment of advanced gynecologic malignancies.

Thirty-two patients with advanced gynecologic malignancies were treated with m-AMSA, 120 mg/m2 intravenously every 3 weeks. Seventeen patients with advanced carcinoma of the cervix who were treated with m-AMSA had a median performance status (CALGB scale) of 2. There were two partial responses (PR) (14%) in 16 evaluable patients. The median duration of survival was 76 days following the initiation of m-AMSA treatment. In ovarian carcinoma, none of the nine evaluable patients who were treated responded. One PR occurred among four treated patients with endometrial adenocarcinoma. Toxicity was limited to myelosuppression (WBC greater than 2500/micrograms in 29/77 courses, WBC greater than 1500/micrograms in 16/77 courses, platelets greater than 100,000/micrograms in 10/77 courses, and drug-induced anemia in 7/77 courses) and mild to moderate nausea and vomiting (10/31 patients). Three patients required hospitalization for fever and granulocytopenia, and one patient died from drug-induced sepsis. Although toxicity was acceptable in this group of heavily pretreated patients, m-AMSA has limited activity in patients with advanced carcinoma of the cervix and no apparent activity in patients with advanced epithelial ovarian carcinomas. Continued trials are indicated in patients with adenocarcinoma of the endometrium.

Adenocarcinoma↗

Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience.

CLM developed in 60 of 526 patients (11%) with SCLC seen at the NCI between August 1969 and June 1980. Life table analysis revealed an overall 25% risk of CLM at 3 years. CLM was diagnosed during all phases of the patients' clinical course, but the majority (83%) were cases diagnosed at the time of progressive systemic disease. Univariate log rank analysis indicated that pretreatment factors associated with the development of CLM included: involvement of the brain, spinal cord, bone marrow, liver or bone; extensive disease; and male sex. Patients who did not obtain a complete response to systemic therapy were at greater risk of developing CLM than complete responders. Multivariate analysis of these factors indicated that liver metastases were most strongly associated with the time to development of CLM, followed in order of importance by bone and CNS metastases. Patients usually presented with signs and symptoms reflecting involvement of multiple areas of the neuraxis including the cerebrum, cranial nerves and spinal cord; 51 of the 60 patients had intracerebral metastases and 27 had spinal cord lesions during their clinical course. Autopsy features including focal or diffuse involvement of the leptomeninges with infiltration of the Virchow-Robin spaces were similar to meningeal lymphoma and leukemia, except that CLM was rarely the sole manifestation of CNS tumor. Median survival following the diagnosis of CLM was 7 weeks. However, most deaths were attributed to systemic disease, and treatment with intrathecal chemotherapy and irradiation often provided palliation. With the increased awareness of this complication, an antemortem diagnosis increased from 39% prior to 1977, to 88% of patients after 1977.

Adult↗

Computed tomographic evaluation of carcinoma of the cervix.

To assess the accuracy of computed tomography (CT) in staging advanced carcinoma of the cervix, 18 staging evaluations were performed in 16 patients with locally advanced (FIGO Stage IB-IVA) cervical carcinoma. CT staging results were compared with the results of clinical staging and postoperative staging. CT was accurate in 12/18 (66%) cases, clinical staging was accurate in 10/18 (55%) cases, and clinical staging with cystoscopy was accurate in 14/18 (78%) cases. CT staging failed to detect microscopic pelvic sidewall involvement and bladder involvement when there was no contrast material in the bladder. In the detection of para-aortic lymph node involvement by tumor, there were 12 true-negative, 4 true-positive, 1 false-positive, and 1 false-negative study (sensitivity = 80%, specificity = 92%). It is concluded that CT is equal in accuracy to other clinical staging techniques and offers the advantage of visualizing the tumor, which allows for more accurate determination of radiation portals.

Carcinoma↗

CT of peritoneal mesothelioma: analysis of eight cases.

In order to define the computed tomographic appearance of mesothelioma, eight patients with histologically proven peritoneal mesotheliomas had computed tomography (CT) performed during the course of their disease. CT findings for all cases were analyzed for evidence of tumor involvement in the peritoneum, mesentery, liver, bone, lymph nodes, and lower pleural space, and for ascitic and pleural fluid. CT findings included evidence of peritoneal involvement (7/8 patients, 88%), ascites (6/8, 75%), mesenteric involvement (6/8, 75%), pleural involvement (4/7, 57%), bone destruction (2/8, 25%), peritoneal mass (1/8, 12%), and retroperitoneal lymph node involvement (1/8, 12%). On the basis of diffuse mesenteric and peritoneal involvement and high incidence of ascites, CT may suggest the diagnosis of peritoneal mesothelioma; however, it may be difficult to differentiate from carcinomatosis, gastrointestinal malignancies, ovarian carcinomas, and, rarely, lymphomas. It is important to suggest the diagnosis of peritoneal mesothelioma because special stains and electron microscopy are necessary for pathologic diagnosis. Experience suggests that CT may be useful in suggesting the diagnosis and biopsy site, and after response to therapy of peritoneal mesothelioma.

Adult↗

Combination chemotherapy for small cell carcinoma of the lung: continuous versus alternating non-cross-resistant combinations.

After stratification for extent of small cell lung cancer, 109 patients were randomized to receive cycles of chemotherapy with cyclophosphamide, doxorubicin, and VP-16-213 [CAVP16 (regimen I)] or to receive CAVP16 to maximum response (minimum of three courses) and then chemotherapy with CCNU, methotrexate, vincristine, and procarbazine (COMP) alternating with CAVP16 (regimen II). A group of patients who achieved complete remission were randomized to receive whole-brain irradiation or to have observation only. Of the 44 patients with limited disease, 28 (64%) achieved a complete remission and 11 (26%) achieved a partial remission. Of the 65 patients with extensive disease, 26 (40%) achieved a complete remission and 28 (46%) achieved a partial remission. There were no significant differences between the regimens in response or survival. The projected median survival times are 14 and 10 months for limited and extensive disease, respectively. Nearly 30% of patients with limited disease will be 2-year, disease-free survivors. Twenty-nine patients were randomized to receive cranial irradiation or observation only; none of the 15 irradiated patients developed cerebral metastases, but five of 14 randomized to observation relapsed in the brain (P = 0.02). One patient died with necropsy evidence of only intracranial disease. The principal hematologic toxic effect was leukopenia. There were 31 febrile episodes (21 infectious) during neutropenia and four toxic deaths. Nonhematologic toxicity was mild. Cranial irradiation in patients who achieve complete remission delays or reduces the incidence of CNS metastases. Although alternating chemotherapy is not beneficial, combination chemotherapy with CAVP16 alone is highly effective treatment modality for small cell.

Adult↗

A phase II trail of vindesine in patients with refractory small-cell carcinoma of the lung.

A phase II study of vindesine at a dose of 3 mg/m2 I.V. for 6 weeks and every other week thereafter was carried out in 18 patients with small-cell carcinoma of the lung. All patients were refractory to conventional therapy and all had been treated previously with spindle inhibitors, vincristine, or VP 16-213. All patients were evaluable for response and toxicity. No objective responses were observed. Leukopenia, the only hematologic toxicity, occurred in 13 patients (72%). Neurotoxicity occurred in five patients (28%). Vindesine appears to have limited activity in patients with small-cell carcinoma of the lung previously treated with spindle inhibitors.

Adult↗

CCNU, vincristine, methotrexate, and procarbazine treatment of relapsed small cell lung carcinoma.

Thirty-two patients with refractory relapsed small cell carcinoma of the lung (SCCL) were treated with a combination of CCNU (lomustine), vincristine, methotrexate, and procarbazine (COMP); 29 were evaluable for response. Nine patients (31%) had responses: five complete responses (CR) and four partial responses. Patients with CR had a median survival of 11 months (range, 51/2-141/2) from the start of COMP. Patients with less than CR had a median survival of approximately 3 months (range, less than 1-7). The comparison of CR versus less than CR is significant (P = 0.003). Patients achieving CR usually had limited disease and four of the five who achieved CR survived greater than 6 months. The regimen was well-tolerated, but myelosuppression was seen in all patients. COMP appears to be a useful combination in patients with relapsed SCCL. Aggressive retreatment should be considered in relapsed patients with this disease since some may achieve a second CR, with the associated potential survival benefit.

Administration, Oral↗

Doxorubicin plus VP-16-213 for the treatment of refractory breast carcinoma.

Thirty patients with refractory advanced breast cancer who had no prior treatment with doxorubicin or VP-16-213 received doxorubicin 45 mg/m2 I.V. on day 1 and VP-16-213 50 mg/m2 I.V. on days 1 through 5. Courses were repeated every 21 days when hematologic recovery permitted. Among 30 evaluable patients, one had a complete response and 11 had a partial response. Four patients had stabilization of their disease. There was thus a 40% response rate with a median response duration of 146 days (range 35-540). Toxicity included moderate to severe myelosuppression, infections, hemorrhage, and mucositis. In these poor prognoses in previously treated patients, the combination of doxorubicin and VP-16-213 appears to be an effective secondary treatment for metastatic breast cancer.

Adult↗

Phase I trial of aclacinomycin A.

Aclacinomycin A (ACM-A), an anthracycline analog, was given to 17 patients with solid tumors and to one patient with multiple myeloma, in a phase I clinical trial. A single dose of 60-120 mg/m2 was given every 3 weeks. Dose-limiting toxicity was myelosuppression, especially thrombocytopenia. Granulocytopenia was variable and did not always recover by Day 21 in time for the next ACM-A treatment. Other toxic effects were nausea, vomiting, urticaria, and elevation of hepatic enzymes. Alopecia was not a side effect, even in patients receiving multiple courses of ACM-A. Nine patients were monitored with 24-hour continuous ECG recordings (Holter) on 19 ACM-A treatment days. The incidence of premature atrial and ventricular beats was significantly increased following ACM-A administration. In addition, one patient developed episodes of high-degree atrioventricular block and complete heart block after each of four ACM-A doses, necessitating the insertion of a pacemaker. No antitumor responses were seen in the ten patients who had measurable disease and who had received two or more courses of ACM-A. The recommended doses for solid tumor phase II studies are 100 mg/m2 as a single dose every 4 weeks for patients with high performance status and minimal prior chemotherapy and 60 mg/m2 every 4 weeks for all other patients. Until the acute cardiac effects of ACM-A are further understood, we recommend that all patients receiving ACM-A be monitored by ECG recordings.

Aclarubicin↗

A clinical program of platelet cryopreservation.

A program of platelet cryopreservation has been developed at the Baltimore Cancer Research Center which now provides substantial proportion of the platelet transfusion requirements of alloimmunized patients. The program has gradually grown in size during the last eight years and in 1979 approximately 1600 units of frozen platelets were transfused including 225 transfusions of autologous platelets administered to 45 patients with leukemia. For many alloimmunized patients autologous frozen platelets represented the only source of histocompatible platelets. 5% dimethylsulfoxide is used as the cryoprotective agent and the platelets can be maintained in the frozen state for at least three years without significant reduction in effectiveness. There are essentially no side effects following transfusion and patient acceptance has been excellent. Post-transfusion increments have been highly consistent during the last five years, averaging two thirds of the recovery obtained with fresh platelets with accompanying shortening of the bleeding time. The technology is simple, cost effective and reproducible and is suitable for use in more general blood bank settings.

Blood Platelets↗

Mitomycin C and vinblastine chemotherapy for advanced breast cancer.

Mitomycin C, 20 mg/m2 day 1, and vinblastine, 0.15 mg/m2 days 1 and 21, were administered intravenously to 31 patients with refractory previously treated advanced breast cancer. Courses were repeated every six to eight weeks when adequate hematologic recovery permitted. Thirty of the 31 patients were evaluable; one had a complete response and 11 had a partial response. Four patients had stabilization of their disease. There was a 12/30 (40%) response rate with a median response duration of 127 days (range 69--412 days). Toxicity included moderate to severe myelosuppression, infections, hemorrhage, neurologic symptoms, pulmonary toxicity and mucositis. In previously treated patients with poor prognoses, the combination of mitomycin C and vinblastine appears to be a worthwhile secondary treatment for metastatic breast cancer.

Adult↗

Leptomeningeal carcinomatosis in small cell carcinoma of the lung.

Among 137 patients with small cell carcinoma of the lung (SCCL) treated on two consecutive protocols, leptomeningeal metastases were documented in 12 patients (9%), 10 antemortem by cerebrospinal fluid (CSF) cytology, one by myelogram, and one only at necropsy. Signs and symptoms included confusion in seven, limb weakness in six, paresthesias in three, headache in two, urinary incontinence in two, and nausea and vomiting, diplopia and neck pain in one patient each. Nine of the 12 patients had evidence of other metastases while three patients relapsed first in the CSF and one had disease only in the leptomeninges. Treatment for this complication including irradiation, intrathecal chemotherapy, or systemic chemotherapy was generally ineffective with a median duration of survival of 50 days (range 5 to 130) after diagnosis of leptomeningeal. Necropsies showed thick tumor deposits along cord, distal nerve roots, cauda equina, and in Virchow--Robbins spaces with deep invasion into adjacent neural substance in six of the seven. Leptomeningeal involvement appears to have become manifest as median survival has increased. CSF cytology should therefore be examined in patients who develop unusual neurological findings during the course of this disease and methods of prevention may need to be considered in future studies.

Carcinoma, Small Cell↗