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Biomedical subjects

B S Yap

Publications and source records attributed to B S Yap.

34 records · Page 2Linked to original sources

CSF carcinoembryonic antigen in meningeal carcinomatosis from breast cancer.

Levels of CSF carcinoembryonic antigen (CEA) were determined in 23 patients with breast cancer and meningeal carcinomatosis. Levels greater than 1.5 ng/mL were observed in 16 patients; seven patients had undetectable levels. The meningeal disease of seven patients with elevated CSF CEA levels completely responded to treatment, and their CSF CEA levels concurrently decreased. Two patients whose meningeal disease responded poorly to treatment had persistently elevated levels of CSF CEA. In two other patients, a rising CSF CEA level was detected before there was any other evidence of meningeal relapse. Serial measurement of CSF CEA may play an important role in the clinical management of meningeal carcinomatosis in patients with breast cancer.

Breast Neoplasms↗

Sarcoma of the stomach: clinicopathologic study of 43 cases.

The records of 43 patients with histologically proved primary gastric sarcoma treated at M. D. Anderson Hospital and Tumor Institute between 1945 and 1975 were reviewed. Weight loss, abdominal pain, and hematemesis or melena were the most common symptoms, and palpable epigastric mass was the most common physical sign. Ninety-five percent of the gastric tumors were leiomyosarcomas. The median survival time and the five-year survival for the 29 patients who had curative gastrectomy were 33 months and 38%, respectively. Morphologic and histologic factors that adversely influenced the length of disease-free interval and survival following curative surgery included 1) primary tumor 8 cm or greater in diameter, 2) tumor extension to serosa of the stomach, and 3) low grade of differentiation of the primary tumor. Seventy-seven percent of recurrences in patients with curative tumor resection occurred within two years of resection of the primary. Of the 17 patients with advanced disease who received chemotherapy, two (15%) had objective tumor regression of greater a median survival time of eight months for patients who failed to respond. New approaches that may improve the results of treatment of gastric sarcoma are discussed.

Female↗

Cyclophosphamide, vincristine, adriamycin, and DTIC (CYVADIC) combination chemotherapy for the treatment of advanced sarcomas.

One hundred and forty adult patients with advanced sarcomas (125 soft tissue and 15 bone) were treated with a combination chemotherapy regimen consisting of cyclophosphamide, vincristine, Adriamycin, and DTIC (CYVADIC). There were 21 (15%) complete and 45 (32%) partial responders, with an overall response rate of 47%. The response rate was 50% (17% complete) for patients with soft tissue sarcomas compared with 20% (none complete) for patients with bone sarcomas. The median duration of response was 9.5 months (range, 1-40+ months) for complete responders and 7 months (range, 1-31 months) for partial responders. The median time to achieve response was 9 weeks and the median number of courses of therapy to response was three. The median survival time was 16 months for responders compared with 7 months for nonresponders (P = 0.001). The most responsive tumor types were neurofibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, fibrosarcoma, and angiosarcoma. Pulmonary and soft tissue metastases were more responsive than bone and liver metastases. CYVADIC toxicity was predominantly limited to myelosuppression, vomiting, fever of unknown origin, and neuropathy. CYVADIC is an effective combination chemotherapy regimen in the treatment of advanced sarcomas.

Antineoplastic Agents↗

Clinical pharmacology of IMPY by radioimmunoassay.

A radioimmunoassay for IMPY has been developed using [3H]acetyl-IMPY and antibody induced by immunizing rabbits with succinyl-IMPY bovine serum albumin conjugates. The method was reproducible and sensitive at a dose of 0.2 microgram/ml. The cross-reactivities of IMPY and IMPY derivatives with the antibody were compared. Using this radioimmunoassay, clinical pharmacology was performed in cancer patients during phase I trials. Following 30-60-minute iv infusions of IMPY (450-1500 mg/m2/day for 5 days), the drug disappeared rapidly from plasma with an initial half-life of less than 10 minutes and second half-life of 4 hours. The half-lives are not affected by minimally abnormal hepatic function and are not dose-related. The apparent volume of distribution was approximately 125 ml/kg. The results obtained on Day 5 were essentially the same as those obtained on Day 1. IMPY was also detected in glioblastoma, brain, and temporalis muscle when the drug (500 mg/m2) was infused iv 4-5 hours before surgery. The tissue drug levels were comparable to or higher than those of plasma. The drug was also measurable in kidney and liver tissues obtained 4 hours after death in a patient who died 21 hours after iv infusion of IMPY at a dose of 1500 mg/m2/day for 3 days.

Antineoplastic Agents↗

High-dose methotrexate for advanced breast cancer.

High-dose infusions of methotrexate with citrovorum factor rescue were evaluated in 27 patients with advanced recurrent breast cancer who had previously been treated with various Adriamycin-containing regimens. Eight of 27 patients (29%) achieved objective tumor regression with a median duration of response of 26 weeks. Nineteen patients had previously received standard doses of methotrexate (less than 50 mg/m2/dose), while eight patients had had no prior exposure to methotrexate. The response rates observed in these two groups of patients were similar. Except for two drug-related deaths, toxic effects were acceptable. Myelosuppression was mild, transient, and noncumulative. Gastrointestinal toxic effects did not appear to be dose-related and were mild in most instances. Central nervous system dysfunction with lethargy, fatigability, confusion, and disorientation was the most significant toxic effect of this high-dose methotrexate therapy and was observed in six (22%) of the patients. In two patients treatment with this program was discontinued because of the development of renal dysfunction. High-dose methotrexate with citrovorum factor rescue appears to be an effective regimen in patients with advanced refractory breast cancer. However, in view of the enormous cost necessitated by this treatment approach, we do not feel further studies would be worthwhile.

Age Factors↗

Oropharyngeal candidiasis treated with a troche form of clotrimazole.

A randomized double-blind trial was conducted to assess the local effectiveness and safety of a troche form of clotrimazole in the treatment of oropharyngeal candidiasis in cancer patients. One half of the patients received one 10-mg troche and the other half received one 50-mg troche, five times a day for two weeks. Clinical cures were observed in 50 episodes, resulting in a cure rate of 96%. The median duration of oropharyngeal candidiasis after the start of therapy was three days in those treated with the 50-mg troche and four days in those who had received the 10-mg troche. Side effects were minimal, and only one patient experienced nausea and abdominal pain. Both the 10-mg and 50-mg troches appear to be efficacious and safe, but the 50-mg dose may be preferable because it is somewhat more effective without additional toxicity.

Administration, Oral↗

Netilmicin in the treatment of infections in patients with cancer.

Ninety-two patients with cancer with 100 infectious episodes were treated with netilmicin sulfate, a new aminoglycoside. Netilmicin was administered intravenously, either intermittently or by continuous infusion. The overall cure rate was 60%. Gram-negative bacilli were the most common causative organisms and the response rate for these infections was 32/53 (60%). The most common pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia, urinary tract infection, and septicemia were the most common types of infection treated and the response rates were 23/47 (49%), 19/21 (90%), and 9/17 (53%), respectively. Nephrotoxicity occurred in ten patients (6%) who had normal renal function initially. Netilmicin is an effective aminoglycoside with a spectrum of antibacterial activity similar to that of gentamicin sulfate and it appears to be less nephrotoxic.

Bacterial Infections↗

Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate.

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.

Acute Disease↗

Meningeal carcinomatosis in breast cancer.

Twenty-five breast cancer patients with meningeal carcinomatosis seen over a period of 16 months were reviewed. In all cases, the clinical diagnosis was made in the presence of diverse neurological manifestations by the demonstration of malignant cells in the cerebrospinal fluid. In ten patients, the clinical diagnosis was documented at autopsy. All patients were receiving systemic chemotherapy at the time the diagnosis of meningeal carcinomatosis was made. In 9 of the 25 patients, meningeal involvement was associated with progression of systemic metastases, while 5 exhibited stable or partial remission from systemic metastases and 7 were in complete remission at the time of their CNS relapse. CNS involvement was the first manifestation of recurrent disease from breast cancer in 4 of 25 patients. Meningeal involvement can, therefore, occur at any time during the course of breast cancer. With increasing diagnostic awareness and the employment of several therapeutic strategies, the prognosis of these patients, though poor, was significantly improved over that of historical control patients.

Adult↗

The value of adriamycin in the treatment of diffuse malignant pleural mesothelioma.

Thirty-six patients with diffuse malignant pleural mesothelioma were seen over a period of 15 years. The median age was 60 years (range, 21 to 75 years), and the male to female ratio was 2.3 to 1. The most common symptoms were chest pain and shortness of breath and all patients presented with pleural effusion on chest x-ray. The diagnosis was established by tissue biopsy in all cases. The median survival time for all patients was 12.5 months. Twenty-one patients were treated with an adriamycin-containing regimen and in this group, the median survival time from histological diagnosis was 14 months. In contrast, the median survival time for the 15 patients, who did not receive adriamycin, was 6 months (p = 0.009). The median survival time from the initiation of chemotherapy was 9 months for the adriamycin group and 2 months for patients treated with other type of chemotherapy (p = 0.001). Adriamycin appears to be of benefit in the treatment of diffuse malignant pleural mesothelioma.

Adult↗

Clinical pharmacology of netilmicin.

Pharmacological studies of netilmicin were conducted in 30 cancer patients. After intravenous administration of 50 mg of netilmicin or gentamicin per m(2) over a 1-h period in 10 patients, the mean peak serum concentrations occurred at the end of the infusion and were 7.6 and 7.3 mug/ml, respectively. At 6 h, the mean serum concentrations of both drugs was 1.1 mug/ml. After intramuscular injection of 50 mg of netilmicin per m(2) to each of the same 10 patients, the mean peak serum concentration was 5.5 mug/ml and occurred at 1 h, and, at 6 h, the mean serum concentration was 1.4 mug/ml. The mean proportion of netilmicin excreted in urine during 6 h after intramuscular injection was 55%, and after intravenous injection it was 40.9%. Results were similar with gentamicin sulfate. After administering 60 mg of netilmicin per m(2) intravenously over 30 min every 6 h in 9 patients, the mean peak serum concentration (7.9 mug/ml) occurred at the end of the infusion. The concentration gradually decreased to below 2.0 mug/ml after 4 h. Continuous infusion of 60 mg of netilmicin per m(2) every 6 h after a 60-mg/m(2) loading dose in 11 patients produced levels consistently above 2.9 mug/ml, during the initial 6-h infusion, and levels above 2.0 mug/ml for at least 1 week.

Adult↗

Phase I clinical evaluation of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole.

2,3-Dihydro-1H-imidazo[1,2-b]pyrazole, a DNA synthesis inhibitor, was given to 25 patients in a phase I study. The drug was administered by rapid iv infusion daily x 5 days at 3-week intervals at doses ranging from 150 to 1500 mg/m2/day. Side effects were observed with doses of greater than or equal to 1000 mg/m2/day and included nausea and vomiting, diarrhea, dark urine, and anemia. At doses of 1500 mg/m2, three patients had evidence of hemolysis (two had hemoglobinuria and one had acute intravascular hemolysis). The hemolysis was severe enough to cause death in one patient and necessitated abandoning further dose escalation. There was minimal or no myelosuppression at any dose level. No objective tumor regression was observed in any of the 16 patients evaluable for response. Further studies are recommended to carefully evaluate the etiology of the hemolysis before proceeding to a phase II trial. It is unlikely that this drug will prove to be useful unless methods for circumventing hemolysis are developed.

Adult↗

Phase II evaluation of AMSA in adult sarcomas.

AMSA an acridine derivative, was administered to 35 adults with previously treated advanced sarcomas. Patients with adequate bone marrow reserve received 120-150 mg/m2 of AMSA as a single dose repeated every 3 weeks. Patients with inadequate bone marrow reserve received 100-120 mg/m2 of AMSA. Among 31 evaluable patients, there was one partial response that lasted 6 months in a patient with intra-abdominal malignant fibrous histiocytoma with liver metastases. Thirteen patients had stable disease with a median time to disease progression of 5 months (range, 2-13), while 17 patients demonstrated progressive disease with a median time to disease progression of 2 months (range, 1-3). The median survival time for the 31 evaluable patients in this study was 5 months. The toxic effects were mild and included myelosuppression, nausea and vomiting, fever of unknown origin, and fatigue. At the dose and schedule used in this study, AMSA does not appear to have any significant activity in advanced sarcomas of adults.

Adolescent↗

Phase I--II study of 3-deazauridine in adults with acute leukemia.

3-Deazauridine, a uridine analog, was administered to 36 patients with acute leukemia by both intermittent and continuous iv infusion at doses ranging from 400 to 6000 mg/m2/day x 5, repeated at 1--3-week intervals. There were no complete or partial responses but three patients showed hematologic improvement. Major toxic effects were myelosuppression, stomatitis, vomiting, diarrhea, and skin erythema. Daily doses greater than 3000 mg/m2 were associated with significantly increased toxicity, including three drug-related deaths. The recommended dose for future studies is 2500 mg/m2/day as a continuous 5-day infusion.

3-Deazauridine↗