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Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 145 records · Page 8Linked to original sources
PubMed1990

Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial.

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.

Administration, Oral↗
PubMed1990

High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Randomized comparison of two combination regimens versus minimal chemotherapy in nonsmall-cell lung cancer: a Southeastern Cancer Study Group Trial.

Patients with advanced nonsmall-cell lung cancer (NSCLC), good performance status, and no prior chemotherapy were randomized to receive one of three regimens: intravenous vindesine (V) 3 mg/m2 every 2 weeks; V 3 mg/m2 weekly for 5 weeks, followed by a dose every 2 weeks plus mitomycin (VM) 20 mg/m2 day 1 and then 15 mg/m2 every 6 weeks; or V at the more intensive dose rate plus cisplatin (VC) 120 mg/m2 with forced diuresis on days 1 and 29 and then every 6 weeks. A total of 435 patients were enrolled in the trial, with 410 (94%) assessable for prognostic characteristics and survival. Among the 375 patients assessable for response, only 58 (15%) achieved objective response. Single-agent V every 2 weeks was inactive (response rate less than 1%), effectively acting as a no-treatment arm. Among assessable patients receiving VM, 33 (27%) responded; among patients receiving VC, 24 (19%) responded. There was no statistically significant survival difference among the treatment arms, with median survival among those treated with V 14.8 weeks, VM 20.4 weeks, and VC 24.7 weeks; VC achieved borderline significance (P = .06) compared with V. In a prognostic factor analysis, treatment was not a significant factor (P = .447) for survival. Thus, in this large multicenter trial, neither a high-dose cisplatin combination nor a noncisplatin regimen (VM) with a comparable response rate had a significant survival advantage over minimal chemotherapy. New approaches are needed in advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Etoposide kinetics in patients with obstructive jaundice.

The kinetics and urinary excretion of etoposide and etoposide glucuronide were determined in 11 patients with obstructive jaundice (bilirubin greater than 2.0 mg/dL) and in 23 patients with normal renal and hepatic function. Mean (+/- SE) measurements of clearance (24.5 +/- 2.06 v 26.5 +/- 2.05 mL/min/m2), half-life (5.7 +/- 0.5 v 6.4 +/- 0.5 hours), and volume of distribution (12.4 +/- 1.1 v 13.7 +/- 1.6 L/m2) were not significantly different in patients with jaundice when compared with controls. Similarly, etoposide kinetics in three patients determined during a period of hyperbilirubinemia were not different from measurements made in the same patients following resolution of their obstructive jaundice. In patients with jaundice, 46% of an administered etoposide dose was excreted in the urine as etoposide compared with 35% in controls (P = .15). Urinary excretion of etoposide glucuronide accounted for 29% of an administered etoposide dose in control patients and 15% in those with hepatic obstruction (P = .03). Biliary etoposide excretion measured in four patients with T-tubes was insignificant (less than 2.0% of an administered dose). The calculated renal clearance of etoposide was 11.5 mL/min/m2 in patients with jaundice and 10.4 mL/min/m2 in controls (P = .53). Respective metabolic clearance was 4.9 and 6.9 mL/min/m2 in these two study groups (P = .13). Although hepatic metabolism of etoposide may be slightly decreased in patients with obstructive jaundice, a modest increase in renal etoposide excretion appears to compensate for this change, so that total clearance is similar in the patients with jaundice when compared with controls. No etoposide dose reductions appear to be needed in treating patients with obstructive jaundice who have normal renal function.

Biliary Tract↗
PubMed1990

Chronic daily administration of oral etoposide.

Etoposide is a useful antineoplastic drug, but its optimal dose and schedule of administration remain unknown. In small cell lung cancer (SCLC), an intravenous dose given on a 5-day schedule is clearly superior to the same dose given over 1 day. The standard dose has been in the range of 300 to 500 mg/m2 divided over 3 to 5 days. Whether this schedule dependency (superiority) extends beyond 5 days is unknown. We have investigated patients with several refractory neoplasms who were given oral etoposide over a long-term period (21-day cycles) in a phase 1 trial. The maximum tolerated dose is 50 mg/m2/d for 21 days. The major toxicity is myelosuppression, which usually resolves by days 28 to 35. Responses were seen in several patients. Phase II trials are under way, and it appears that the long-term daily administration of etoposide is more active than the standard schedule. Responses have been seen in refractory germ cell tumors, lymphomas, and SCLC in patients who have progressed on the standard dose and schedule of etoposide. In addition, the drug may be active in soft tissue sarcoma. Preliminary results of combination chemotherapy with cisplatin show good tolerance and activity. The long-term daily administration of etoposide may prove to be a superior schedule and, as such, may be incorporated into combination chemotherapy for several neoplasms.

Adult↗
PubMed1990

Primary brain lymphoma in the immunocompetent host: relation to Epstein-Barr virus.

Epstein-Barr virus has been implicated in the pathogenesis of primary brain lymphoma in patients with congenital or acquired immunodeficiency states. To examine its role in central nervous system (CNS) lymphoma in the immunocompetent host, Epstein-Barr virologic studies were performed in six consecutive cases seen at our institutions. Virus DNA sequences were detected in only one of three tumor specimens studied by Southern blot hybridization. Serologic studies from the entire cohort disclosed past virus infection; however, antibody reactivity to virus-specific antigens in cerebrospinal fluid was limited to the patient harboring genome-positive tumor. Immunologic studies revealed hyperimmunoglobulin-E (range, 720 to 1040 micrograms/ml) in each of four patients tested. Our findings suggest that Epstein-Barr virus is an infrequent pathogen in nonimmunosuppressed patients with primary CNS lymphoma. Abnormalities in isotype-specific regulation of IgE production are common in such patients and may have pathogenetic implications.

Aged↗
PubMed1990

Appetite stimulation and weight gain with megestrol acetate.

The extreme anorexia and cachexia associated with cancer and other disease states often have important physical and psychologic impact on both patients and their families. Weight gain resulting from megestrol acetate therapy in breast cancer patients suggests that progestins may be useful for alleviation of disease-associated appetite and weight loss. Early breast cancer experience, as well as preliminary data from a randomized, placebo-controlled trial of high-dose megestrol acetate in cancer anorexia and wasting, is therefore reviewed. Although the precise mechanism by which megestrol acetate exerts its effect remains unclear, weight gain was observed in 75% of patients in the high-dose study and in nearly all of those who remained on therapy for 6 weeks. It was concluded that, although megestrol acetate cannot be expected to directly affect the prognosis of patients with hormone-insensitive tumors, it may increase host resistance by improving nutritional status and/or enhancing the quality of life.

Adult↗
PubMed1989

Phase I clinical study of N-[(4-chlorophenyl)amino]carbonyl-2,3-dihydro-1H-indene-5-sulfonamide (LY186641).

Between February 1987 and July 1988, 45 patients with advanced refractory cancer were treated with LY186641, a diarylsulfonylurea that has shown a broad spectrum of activity in preclinical testing. Patients received a weekly p.o. dose of LY186641 for 6 consecutive weeks; responding and stable patients continued weekly therapy until progression occurred. Using a standard phase I study design, the first three patients received LY186641 at 30 mg/m2 week; the dose was escalated in subsequent patients until dose-limiting toxicity occurred. Methemoglobinemia was the major toxicity observed and was dose related. Methemoglobin levels peaked approximately 24 h after LY186641 was administered and fell to low levels after 48 h. Six patients developed fatigue, cyanosis, and dyspnea associated with serum methemoglobinemia levels of greater than 20%; four of these patients were subsequently removed from the study. Hemolytic anemia was also observed but was clinically significant in only 10 patients. Other side effects were mild and infrequent. The maximum tolerated dose of LY186641, when given at this schedule, was 2550 mg/m2/week. No objective tumor responses were observed.

Antineoplastic Agents↗
PubMed1989

Peritoneal carcinomatosis of unknown primary site in women. A distinctive subset of adenocarcinoma.

STUDY OBJECTIVE: To define the clinical features and results of systemic treatment in women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surfaces. DESIGN: Retrospective analysis of 18 patients treated at a single institution between 1978 and 1984. PATIENTS: All 18 women had abdominal carcinomatosis and had no primary site identified at laparotomy. Nine patients had limited residual tumor (maximal tumor diameter, 3 cm or less) after initial cytoreductive surgery, and 9 patients had extensive residual disease. INTERVENTIONS: In general, patients were treated according to standard guidelines for treatment of advanced ovarian carcinoma. All patients had initial laparotomy with attempted cytoreduction; of these 18 patients, 16 subsequently received cisplatin-based chemotherapy. Patients were restaged either clinically (10 patients) or with second-look surgery (8 patients). RESULTS: The median survival for all patients was 23 months. Five patients had complete response to chemotherapy, and three patients remain disease-free 41, 59, and 77 months after diagnosis. Patients with limited residual disease had longer median survival than did those with extensive residual disease (31 months compared with 11 months). CONCLUSIONS: Women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surface should be distinguished from other patients with adenocarcinoma of unknown primary site because they have a more indolent disease course, a higher response rate to systemic therapy, and a chance for long-term, disease-free survival after therapy. Although optimal treatment is undefined, we recommend that these patients be treated using the guidelines established for therapy of advanced ovarian carcinoma, including initial surgical cytoreduction followed by cisplatin-based combination chemotherapy.

Adenocarcinoma↗
PubMed1989

Chemotherapy of advanced non-small-cell lung cancer: a randomized trial of three cis-platin-based chemotherapy regimens.

One hundred fifty-two patients with locally advanced or metastatic non-small-cell lung cancer were randomized to receive treatment with one of three cis-platin-containing chemotherapy regimens: vindesine/cis-platin, etoposide/cis-platin, or vindesine/etoposide/cis-platin. Following an 8-week induction course of treatment, patients were evaluated for response; responders continued to receive monthly chemotherapy. All patients were followed until death. Response rates for the three regimens were 10%, 6%, and 24%, respectively; the cis-platin/vindesine/etoposide regimen produced more responses than did either cis-platin/etoposide or cis-platin/vindesine (p less than 0.05). However, median survival was not improved with the three-drug regimen, and myelosuppression produced by this regimen was worse. The 20-week median survival for the entire group suggests that these treatments had no impact on survival. None of these regimens can be recommended for routine treatment of patients with advanced non-small-cell lung cancer. The addition of vindesine did not make a significant impact in response rate or overall survival in this study.

Actuarial Analysis↗
PubMed1989

Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol.

Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Chronic daily administration of oral etoposide--a phase I trial.

In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16.

Administration, Oral↗
PubMed1989

Combined small-cell and non-small-cell lung cancer.

Nine (2%) of 429 small-cell lung cancer (SCLC) patients seen at Vanderbilt University between 1977 and 1983 had a combined subtype SCLC at diagnosis (ie, small-cell carcinoma plus squamous cell or adenocarcinoma). Staging procedures and chemotherapy treatment were uniform for all 429 patients. The diagnosis of combined histology was established via bronchoscopy (six patients), needle aspiration biopsy (one), lymph node biopsy (one), and thoracotomy (one). The clinical characteristics of the combined subtype patients were similar to patients with other subtypes of SCLC (ie, there were no differences in median age, sex, performance status, and stage of disease). However, patients with a combined subtype histology had a higher incidence of peripheral lesions on chest x-ray (56% v 14%, P less than .001) and a lower median lactate dehydrogenase (LDH) (301 IU/L v 341 IU/L, P = .0002) at diagnosis. The overall response to chemotherapy (57% v 78; P = .5) and the median survival (8 months v 10 months; P = .4) of the combined subtype patients were similar to patients with other subtypes of SCLC. Two (22%) combined histology patients survived greater than or equal to 5 years. Both had had surgical resection in addition to chemotherapy. These data suggest that the combined subtype of SCLC is clinically similar to pure SCLCs and that surgery may play a prominent role in the management of these tumors. The possibility of a combined histology tumor should be considered in patients thought to have SCLC on the basis of limited biopsy material, such as a needle aspiration or bronchial biopsy, and when the primary lesion is peripherally located on chest x-ray.

Adenocarcinoma↗
PubMed1989

The management of patients with adenocarcinoma and poorly differentiated carcinoma of unknown primary site.

Patients with metastatic carcinoma of unknown primary site form a heterogeneous group, and optimal management of these patients requires the recognition and identification of treatable subsets within this large group. A large percentage of these patients have well-differentiated adenocarcinomas of unknown primary site. Although many of these patients currently have unresponsive neoplasms and short survival expectations, certain identifiable subsets respond well to systemic therapy, with prolongation of survival and, in some cases, cure of their malignancies. Patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site make up a substantial minority of all these patients and require careful evaluation. Specialized pathologic evaluation, including immunoperoxidase staining and electron microscopy, is often helpful in diagnosis. Careful clinical evaluation, including staging with chest and abdominal computed tomography scans, and measurement of serum human chorionic gonadotrophin and alpha-fetoprotein, is also important. In some patients, no diagnosis more specific than "poorly differentiated carcinoma" can be made; these patients often respond well to cisplatin-based chemotherapy, particularly if the tumor is located in the mediastinum, retroperitoneum, or lymph nodes. Another responsive subset of patients are those with neuroendocrine differentiation identified either by electron microscopy or immunoperoxidase staining. These patients also respond to systemic chemotherapy, and some have the opportunity for long-term survival.

Adenocarcinoma↗
PubMed1988

Late recurrences in long-term survivors of germ cell neoplasms.

Patients with germ cell neoplasms who are in complete remission 2 years after treatment have a very high probability of cure, and reports of recurrences occurring after 2 years are rare. Of 81 testicular cancer patients treated for advanced disease at Vanderbilt University between 1970 and 1985, five developed a recurrent or metachronous germinal tumor 58 to 195 months after the initial treatment. Only two of these patients had received prior cisplatin-based combination chemotherapy. Four patients had unfavorable prognostic features when tumor recurrence was diagnosed. All five patients responded to salvage chemotherapy, although there were only two complete responses. The extent of disease was a significant factor in predicting response to salvage therapy. The possible mechanisms of development of a late recurrence of germinal neoplasms include the following: (1) malignant degeneration of mature teratoma to germinal malignancy; (2) growth of an occult testicular tumor not eliminated by chemotherapy due to the presence of a blood-testicular barrier; (3) development of a second primary germ cell neoplasm; or (4) late relapse due to persistent microscopic viable tumor with an atypical less aggressive biologic behavior. "Cured" germ cell tumor patients need careful follow-up beyond 2 years. At a minimum, these patients should be seen annually. Patients found to have teratomas following cisplatin-based chemotherapy should probably undergo more frequent evaluations.

Adult↗
PubMed1988

Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity.

Twenty-nine patients with poorly differentiated neuroendocrine tumors of unknown primary site were seen at Vanderbilt Medical Center between May 1977 and February 1987. All patients had pathologic findings typical of neuroendocrine tumors by electron microscopy (22 patients), light microscopy (6 patients), or immunochemical staining (1 patient). Patient age ranged from 18 to 77 years; 21 were men and 8 were women; and 12 had no history of tobacco use. Seventeen patients had metastatic tumor at two or more locations. Common metastatic sites included the retroperitoneum, lymph nodes (particularly cervical), and mediastinum. In most patients, these neoplasms showed an aggressive biology, with rapid onset of symptoms and rapid growth of metastases. Major responses were seen in 18 of 25 patients who received combination chemotherapy; 6 patients achieved a complete response. Three patients remain disease-free more than 24 months after completing therapy. Four patients with single sites of disease received local therapy only; all remain disease-free 1 to 10 years after completion of therapy. In 4 patients, specific tumor types were eventually recognized: small cell lung cancer, 1; gastrointestinal carcinoid tumor, 2; and extragonadal germinal tumor with predominant neuroendocrine differentiation, 1. In the remaining 25 patients, no well-recognized type of neuroendocrine tumor was identified. Recognition of these tumors broadens the spectrum of neuroendocrine neoplasia, and also identifies a distinct subset of patients with poorly differentiated carcinoma of unknown primary site. Although optimal therapy remains undefined, these patients are usually responsive to combination chemotherapy, and long-term survival is attainable in a minority.

Adenocarcinoma↗
PubMed1988

Curative combination chemotherapy for patients with advanced poorly differentiated carcinoma of unknown primary site.

We have previously reported complete responses and long-term survival following cisplatin-based combination chemotherapy in some patients with advanced poorly differentiated carcinomas of unknown primary site. In order to better define the clinical and pathologic characteristics of the chemotherapy-responsive subgroup, we have reviewed the case histories of our 32 patients who achieved complete response to combination chemotherapy. Initial light microscopic diagnoses were as follows: poorly differentiated carcinoma (23 patients), poorly differentiated adenocarcinoma (eight patients), or poorly differentiated large cell carcinoma (one patient). The median age was 37 years (range, 19-70); 25 of 32 patients were male. All patients had unresectable neoplasms at the time of diagnosis. Twenty-two patients had metastases at two or more locations. In 27 of 32 patients (84%), the predominant site of tumor involvement was either in the mediastinum, retroperitoneum, lymph nodes, or lungs. Six patients were assigned more specific diagnoses at some time during their clinical course on the basis of further pathologic evaluation, additional biopsy material, or autopsy: germinal tumors, two patients; adenocarcinoma of the lung, one patient; carcinoid tumor of the lung, one patient; and malignant melanoma, two patients. Eighteen patients (56%) remain continuously disease free at a median of 77 months following diagnosis and are considered unlikely to recur. All patients with poorly differentiated carcinomas and tumor location in the mediastinum, retroperitoneum, lungs, or lymph nodes should be considered for treatment with intensive cisplatin-containing combination chemotherapy, since some of these patients have potentially curable malignancies.

Adenocarcinoma↗