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Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 235 records · Page 13Linked to original sources
PubMed1984

Pharmacokinetics of high-dose etoposide (VP-16-213) administered to cancer patients.

Plasma urine, and cerebrospinal fluid etoposide concentrations have been measured in 12 adult patients after administration of high-dose (400 to 800 mg/sq m) etoposide in order to determine the pharmacokinetics of this drug at these elevated dosages. Increasing the drug dosage produced proportionally higher peak plasma etoposide concentrations (27 to 114 micrograms/ml) and total areas under the concentration-time curve (9,200 to 48,000 micrograms/ml X min). The etoposide mean (+/- S.D.) terminal half-life of 8.05 +/- 4.3 hr and plasma clearance of 28.0 +/- 9.7 ml/min/sq m, however, were independent of the dosage given. The mean etoposide renal clearance in 5 patients was 10.0 +/- 4.3 ml/min/sq m, representing from 35 to 40% of the total clearance of this drug from plasma. Cerebrospinal fluid etoposide concentrations ranged from 0.1 to 1.4 micrograms/ml, as measured in 6 patients at 1 to 8 hr after high-dose etoposide therapy, and were 1.8 +/- 1.7% of the simultaneously measured plasma levels. Pleural fluid removed from one patient at 18 hr posttherapy contained etoposide at 1.8 micrograms/ml. Our data, combined with data published previously, indicate that the pharmacokinetics of high-dose etoposide is linear within the dosage range tested and similar to that seen with lower drug doses. They also suggest that etoposide penetrates poorly into the cerebrospinal fluid.

Etoposide↗
PubMed1983

Management of the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer.

From 1976 to 1980, 18 of the 250 patients (7%) seen with small cell carcinoma of the lung had clinically evident inappropriate secretion of antidiuretic hormone (ADH). Hyponatremia was usually severe (116 +/- 7 meq/l), and eight patients showed symptoms of water intoxication at the time of diagnosis. Of the eight patients who had plasma ADH measured at diagnosis, seven had elevated values (mean 52.0, range 16.1 - greater than 250 pg/ml). Intensive combination chemotherapy produced objective tumor responses in all patients, and syndrome of inappropriate ADH secretion (SIADH) resolved in 16 of 17 evaluable patients within three weeks of initiation of treatment. ADH values after therapy were normal, and all patients maintained a normal serum sodium during the period of tumor remission in spite of unrestricted fluid intake. All 17 evaluable patients have developed progressive cancer, but only 10 have manifested recurrent SIADH. Patient survival was similar to the overall population of small cell carcinoma patients without SIADH. The indirect methods of treatment for SIADH (fluid restriction, demeclocycline, lithium, urea) are frequently of transient value while awaiting a response to chemotherapy or in patients with resistant tumors. However, the initial treatment of choice for SIADH associated with small cell carcinoma of the lung is combination chemotherapy.

Adult↗
PubMed1983

Testicular germ cell neoplasms.

Rapid progress in the management and treatment of testicular germ cell neoplasms has been made during the last 20 years. The development of sensitive radioimmunoassays for the serum tumor markers alpha-fetoprotein and the beta subunit of human chorionic gonadotropin has greatly aided in the diagnosis, staging, and treatment of nonseminomatous neoplasms. The development of effective combination chemotherapy for nonseminomatous germ cell tumors represents the major advance, and has changed a disease that formerly had a 75 percent two-year mortality to one with a 75 percent cure rate. Cis-platinum, vinblastine, and bleomycin have formed the basis of the most effective regimens. All patients should be treated with curative intent, preferably at an academic center by experienced medical oncologists. Toxicity, particularly myelosuppression, with effective regimens has been significant, but is manageable in most cases. If feasible, surgical removal of residual disease should be considered in patients failing to achieve complete remission with induction chemotherapy. Prognosis is poor for patients with remaining disease after chemotherapy and surgery, but some have been saved with VP-16-containing regimens. Most seminomas are curable with radiotherapy alone, but patients presenting with advanced disease (stages III and IV) should be treated initially with chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Neoplastic meningitis. Marked variations of cerebrospinal fluid composition in the absence of extradural block.

Cerebrospinal fluid levels of protein, glucose, and malignant cells may differ markedly at different levels of the neuraxis in patients with neoplastic meningitis, even in the absence of an extradural blockage to cerebrospinal fluid flow. The pathogenesis of these differences is unclear, but is probably related to focal disruption of the blood-cerebrospinal fluid barrier produced by neoplastic involvement of the meninges. The clinical implications of this new observation are important. When the diagnosis of neoplastic meningitis is strongly suspected, but malignant cells cannot be demonstrated by repeated examination of lumbar cerebrospinal fluid, samples should be obtained by cisternal tap if the neurologic deficits are manifestations from involvement of the cranial nerves or cerebrum. Similarly, response to intrathecal chemotherapy should be monitored with serial examinations of cerebrospinal fluid obtained from the site of most marked pretreatment abnormality.

Adult↗
PubMed1983

High-dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: a phase I study.

VP-16-213, a congener of epipodophyllotoxin, is a useful chemotherapeutic agent especially against small-cell carcinoma of the lung, germ cell carcinoma, and lymphoma. The standard dose of this drug is limited by myelosuppression. Autologous transplantation of cryopreserved bone marrow assures the restoration of hematopoiesis after marrow ablative cytotoxic therapy. By using this technique, VP-16-213 was dose-escalated using a Fibonacci scheme from the previous highest dose administered to humans (1,500 mg/m2) to 2,700 mg/m2 (900 mg/m2 per day for three consecutive days). At 2,700 mg/m2, severe extramedullary toxicity of the mucous membranes was observed in three of three courses. At the next highest dose (2,400 mg/m2), two of 18 courses (11%, p less than 0.01) resulted in severe mucositis, thus defining this dose as the maximally tolerated dose based on extramedullary toxicities. As anticipated, myelotoxicity was severe but based on the kinetics of marrow recovery, VP-16-213 in these doses appeared not to be marrow ablative. Based on responses observed in this study, high-dose VP-16-213 should be explored in phase II studies or used in combination chemotherapy.

Adolescent↗
PubMed1983

Limited value of CT brain scans in the staging of small cell lung cancer.

Computed tomography of the brain was performed as part of the initial staging evaluation of 84 patients with small cell lung cancer. Brain scans indicative of metastatic disease were obtained in 12 (14%) patients, two of whom had no neurologic signs or symptoms. One of these had no other extrathoracic disease. Brain scans without evidence of metastatic disease were obtained in 72 patients, 58 (80.5%) of whom had no signs or symptoms suggestive of metastatic intracranial disease. In the 14 patients with neurologic symptoms but negative computed tomographic scans, other explanations than brain metastases were found. It was concluded that head scanning is a sensitive and accurate method of detecting central nervous system metastases in patients with small cell lung cancer. However, head computed tomography should not be included as part of the initial staging evaluation of the neurologically asymptomatic patients. In only one of 60 such patients did the brain scan change the initial clinical staging, which included chest films, liver and bone scans, and bone marrow biopsy.

Adult↗
PubMed1983

Resistant gestational choriocarcinoma: successful treatment with vinblastine, bleomycin, and cisplatin (VBP).

Two patients with resistant gestational trophoblastic neoplasms were treated with vinblastine, bleomycin, and cisplatin (Einhorn regimen). Both patients had failed multiple conventional therapeutic regimens including methotrexate, dactinomycin, high-dose methotrexate, and the modified Bagshawe regimen. Both patients achieved complete remissions and remain free of disease at 20 and 33 months following completion of therapy. The combination of vinblastine, bleomycin, and cisplatin is highly active in patients with resistant gestational trophoblastic neoplasms, and should be used as second-line therapy for poor-prognosis patients failing initial treatment.

Adult↗
PubMed1983

Complications of treatment of small cell carcinoma of the lung.

Improvements in therapy for small cell carcinoma of the lung have been achieved with treatment regimens that result in significant toxicity. The workshop of the International Association for the Study of Lung Cancer focused on the following complications of chemotherapy and radiotherapy: leukopenia and resultant infections, esophagitis, pneumonitis and pulmonary fibrosis, cardiac toxicity, second malignancies, neurologic complications, and psychosocial effects. The data regarding the incidence and management of these complications are briefly reviewed, and recommendations for further studies are noted.

Aged↗
PubMed1983

Etoposide-induced hepatic injury: a potential complication of high-dose therapy.

Two cases of toxic hepatitis developing in patients receiving high-dose etoposide (VP-16-213) for refractory germinal neoplasms are described. Each patient received a total cumulative dose of at least 6800 mg/m2. Liver function abnormalities, including hyperbilirubinemia, elevated transaminases, and elevated alkaline phosphatase, became clinically apparent approximately 3 weeks following the last dose of VP-16-213. These abnormalities resolved spontaneously without sequelae over 12 weeks. High-dose VP-16-213 may be associated with hepatic injury.

Adult↗
PubMed1983

Advanced minimal residual ovarian carcinoma: abdominopelvic irradiation following combination chemotherapy.

Seventeen patients with advanced ovarian carcinoma who had minimal residual intraabdominal disease after six months of combination chemotherapy were treated with abdominopelvic irradiation. All 17 patients had residual intraabdominal tumor nodules with a cross-sectional diameter of less than 2 cm. Eleven had only microscopic residual disease at the time of irradiation. Fourteen have relapsed at a median of eight months after the completion of radiotherapy. All but two had intraabdominal recurrences. Myelosuppression was common and severe, causing marked delays or discontinuation of radiotherapy in ten of 17 patients. Patients receiving the entire planned dose of radiotherapy had longer disease-free survival (14 months median) than did patients receiving only partial doses (seven months median). However, six of seven patients receiving full dose irradiation have relapsed. Abdominopelvic irradiation in the schedule employed here is poorly tolerated and is not an effective salvage treatment in patients with limited or microscopic residual tumor following initial combination chemotherapy.

Adenocarcinoma↗
PubMed1983

Phase II study of vinblastine in advanced refractory ovarian carcinoma.

Fourteen patients with advanced ovarian carcinoma previously treated with chemotherapeutic agents including cisplatin were treated with vinblastine 0.1 mg/kg intravenously every week. There were no responses in 13 evaluable patients. The median survival was 19+ weeks following the initiation of vinblastine (VBL) therapy. Toxicity consisted of minimal myelo-suppression (WBC count less than 2500/microliter in 8/78 courses, WBC count less than 1500/microliter in 0/78 courses, platelets less than 150,000/microliter in 0/78 courses), nausea (4/13 patients), vomiting (2/13 patients), neuropathy (4/13 patients), and weakness and fatigue (6/13 and 5/13 patients, respectively). Although data derived from the human tumor stem cell assay (HTSCA) suggest that VBL may be an active agent against previously treated ovarian carcinoma, this study in patients with refractory advanced disease suggests that VBL is inactive (less than 20% response rate with 90% confidence levels) in that setting. Whether significant durable benefit can be achieved with VBL therapy in patients whose tumor is sensitive in the HTSCA remains to be seen.

Adult↗
PubMed1982

Endodermal sinus tumor of the mediastinum.

Endodermal sinus tumor (EST) of the mediastinum is a rare germ-cell neoplasm affecting mainly young adult males. Ten patients with EST were treated with a multimodality approach that included surgery, chemotherapy, and radiotherapy. All patients had relapses after achieving a transient response except one who is still in complete remission more than five years following the diagnosis of the disease. Optimal therapy for this neoplasm has yet to be discovered. The disease is a subset of extragonadal germ cell tumors which appears to be lethal in most cases, particularly when the primary tumor is unresectable. The first case of five-year disease-free survival is described.

Adolescent↗
PubMed1982

Randomized study of high-dose versus low-dose methotrexate in the treatment of extensive small cell lung cancer.

Forty patients with extensive small cell lung cancer randomly received either high-dose or low-dose methotrexate with leucovorin rescue in combination with cycles of cyclophosphamide, doxorubicin, and vincristine alternating with cycles of VP-16, vincristine, and hexamethylmelamine. Nineteen patients were treated with the high-dose methotrexate regimen, and 21 received the low-dose methotrexate treatment protocol; both treatment groups were similar in median age, performance status and spread of disease. Response rates (74 percent for high-dose therapy; 67 percent for low-dose therapy), median survival (nine months versus nine months), and overall survival were similar for the two treatment groups. Myelosuppression was equivalent in both treatment groups but moderate to severe mucositis developed more often when patients were treated with the high-dose methotrexate regimen as compared with low-dose methotrexate therapy (p less than 0.001). Central nervous system recurrences developed after three patients received high-dose methotrexate therapy. This study indicates that when used with other antineoplastic agents, high-dose methotrexate therapy does not improve the remission rate or survival nor does it decrease central nervous system metastasis in patients with small cell lung cancer when compared with standard doses of methotrexate; high-dose methotrexate is associated with greater cost and toxicity.

Carcinoma, Small Cell↗