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Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 217 records · Page 12Linked to original sources

Extensive-stage small-cell bronchogenic carcinoma: intensive induction chemotherapy with high-dose cyclophosphamide plus high-dose etoposide.

Seventeen ambulatory patients with extensive-stage small-cell lung cancer received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg) plus etopside (1,200 mg/m2) followed by four or five cycles of conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV) given every 21 days. No additional chemotherapy was given until relapse or progression was documented. Response was assessed initially after high-dose induction therapy and again after completion of all chemotherapy. After induction therapy, 16/17 (94%) patients had achieved an objective response, including five (29%) complete responses and 11 (65%) partial responses. Two partially responding patients improved to a complete response after CAV, while one partial responder progressed and one patient died of an intercurrent illness while receiving CAV. Thus, the overall response after completing all chemotherapy was 15/16 (94%), including seven (44%) complete responses and eight (50%) partial responses. Median response duration was six months (range, 3 to 11 months), and overall median survival was ten months (range, 2 to 17 months). All 31 courses of induction therapy were associated with leukopenia (less than 1,000/microL), 81% with thrombocytopenia (less than 20,000/microL), and 77% with fever (greater than 38.5 degrees C). Seven episodes of bacteremia and one axillary abscess were documented, and there was one treatment-related death (6%). These toxicities are similar to that produced by high-dose etoposide alone. High-dose cyclophosphamide combined with high-dose etoposide can be administered to ambulatory patients with extensive-stage small-cell lung cancer without requiring bone marrow transplantation to reestablish hematopoiesis. Complete response and median survival rates, however, are similar to those obtained with less intensive therapy.

Adult↗

Lung cancer in Hodgkin's disease: association with previous radiotherapy.

Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970. The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population. The pertinent clinical data from these patients are described and compared to 28 additional patients reported from other institutions. Small-cell lung cancer represented the predominant histologic type of lung cancer encountered in both smoking and nonsmoking patients with HD, accounting for 42% of cases overall and greater than 55% of cases reported in reviews of second malignancies. Tobacco use was noted in only 53% of patients. Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD. Nineteen (68%) of these patients received subsequent chemotherapy salvage. The median age at diagnosis of HD and lung cancer was 39 and 45 years, respectively. The interval between diagnosis of HD and metachronous lung cancer averaged seven years but appeared to vary inversely with age. HD patients treated with supradiaphragmatic irradiation or combined modality therapy may be at increased risk for developing lung cancer. The high frequency of in-field malignancies that we observed and the prevalence of small-cell lung cancer in both smoking and nonsmoking patients suggests that chest irradiation may influence the development of metachronous lung cancer in these patients. The finding of a mean latent interval in excess of seven years emphasizes the need for close long-term observation.

Adenocarcinoma↗

Successful treatment of resistant germinal neoplasms with VP-16 and cisplatin: results of a Southeastern Cancer Study Group trial.

Between July 1979 and May 1982, we treated 45 male patients with refractory germinal neoplasms. All patients had previously received intensive cisplatin-containing combination chemotherapy regimens. Patients received salvage chemotherapy with VP-16 and cisplatin +/- bleomycin +/- doxorubicin. Of 44 evaluable patients, 19 (43%) achieved complete remissions with salvage chemotherapy, 12 (27%) had partial remissions, and nine (21%) had no response. Four patients (9%) were not evaluable for response due to early death or noncompliance but are considered treatment failures. Ten patients (23%) remain alive and continuously disease free 20 to 39 months (median, 29 months) after completion of therapy. Hematologic toxicity was severe, with one death related to sepsis. Bleomycin-induced pulmonary fibrosis occurred in 17 patients with two fatalities. The addition of bleomycin and/or doxorubicin to this regimen increases toxicity and probably does not improve treatment results. Salvage chemotherapy with VP-16 and cisplatin offers potentially curative therapy to men with resistant germinal tumors.

Actuarial Analysis↗

Extrahepatic biliary obstruction caused by small-cell lung cancer.

Twelve patients with small-cell lung cancer seen during a 30-month period had jaundice at diagnosis. Five patients had a pancreatic metastasis resulting in extrahepatic biliary obstruction, and seven had diffuse hepatic metastases without extrahepatic obstruction. All patients with pancreatic masses had complete (or nearly complete) resolution of jaundice and abdominal pain within 3 weeks of starting chemotherapy. Patients with extensive liver metastases usually remained icteric in spite of intensive treatment. Three patients with pancreatic metastases survived more than 12 months after the institution of therapy. No patient presenting with jaundice caused solely by hepatic metastases survived beyond 8 months. Small-cell lung cancer can present with jaundice due to diffuse hepatic parenchymal involvement, which is associated with a poor prognosis, or as a result of extrahepatic biliary obstruction, which has potential for rapid palliation and prolonged survival.

Aged↗

High-dose etoposide (VP-16) in small-cell lung cancer.

Etoposide (VP-16) is one of the most active drugs against small-cell lung cancer. There may be a steep dose-response relationship, and we have explored the use of etoposide as a single agent in a high dose (1,200 mg/m2) without bone marrow transplantation, for patients with very bulky, extensive-stage disease. This therapy is well tolerated in patients having good performance status, with myelosuppression representing the major toxicity. Our data suggest there may truly be a steep dose-response relationship. We have continued to explore intensive induction therapy for selected very poor-prognosis patients by adding high-dose cyclophosphamide (100 mg/kg) to high-dose etoposide. This combination is also very myelotoxic, but quite similar to etoposide alone. Our current study adds cisplatin (120 mg/m2) to the high-dose cyclophosphamide-etoposide schedule in an attempt to take advantage of the synergism seen with these drugs in various other circumstances. This series of studies will give us information regarding the feasibility of intensive induction therapy and provide data for the design of phase III studies.

Adult↗

Cisplatin and etoposide combination chemotherapy for refractory small cell carcinoma of the lung.

Twenty-nine patients with refractory recurrent small cell carcinoma of the lung were treated with cisplatin (40 mg/m2) and etoposide (200 mg/m2) each day for 3 days, repeated every 3-4 weeks. Fifteen of these patients had received etoposide in their original treatment regimen. Fifteen (52%) of all patients had a major response, as did nine (60%) of the patients with prior exposure to etoposide. Myelotoxicity was moderately severe. The median duration of responses was 3 months (range, 6-36 weeks). This study suggests synergism between cisplatin and etoposide. The toxicity seen in this heavily pretreated group of patients suggests that smaller doses be studied in this group. The synergism may be best utilized in the initial regimens against small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Chemotherapy of small-cell lung cancer.

Combination chemotherapy has become the cornerstone of management for patients with small-cell lung cancer. Although the majority of patients are palliated, most continue to die of their disease. Studies designed to improve treatment results and to understand the basic biology of this neoplasm are continuing. Several strategies are now being investigated, including the use of non-cross-resistant chemotherapy, dose intensification, manipulation of the duration of therapy, combined modality therapy, and salvage chemotherapy. Studies in these areas have not yet yielded results that have definitively improved response rates or survival. It appears that further therapy after remission induction has not yet proven beneficial. This paper will review selected areas of therapeutic investigation.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of a luteinizing hormone releasing hormone agonist given during combination chemotherapy on posttherapy fertility in male patients with lymphoma: preliminary observations.

Six men undergoing potentially curative chemotherapy for advanced lymphomas received daily injections (50 micrograms) of an analogue of luteinizing hormone releasing hormone (LH-RHa) in an attempt to protect posttreatment gonadal function. The median duration of combined LH-RHa-chemotherapy administration was 25 weeks (range, 14 to 31 weeks). During the simultaneous administration of LH-RHa and chemotherapy, plasma testosterone levels decreased to subnormal levels, while both follicle-stimulating hormone (FSH) and luteinizing hormone levels declined to the lower limit of normal. All subjects became oligospermic or azoospermic within eight weeks of starting treatment. Following discontinuation of chemotherapy and LH-RHa, both plasma testosterone and LH promptly increased and stabilized within the normal range. FSH progressively increased to a level well above the normal range. Only one patient has recovered evidence of active spermatogenesis at 84 weeks postcessation of chemotherapy. No untoward side effects due to LH-RHa were experienced. Although LH-RHa can be administered safely during combination chemotherapy, no improvement in posttreatment fertility has yet been demonstrated.

Adolescent↗

Macro creatine kinase type 1 with electrophoretic mobility identical to that of the MB isoenzyme.

We describe the case of an elderly woman whose symptoms and electrocardiographic pattern initially suggested acute myocardial infarction. The value for total serum creatine kinase (EC 2.7.3.2; CK) was 737 U/L (reference interval: 22-269 U/L), and electrophoresis for CK isoenzymes demonstrated two bands, the more anodal migrating to the CK-MB region and the second migrating between the CK-MB and CK-MM regions. The above-normal total CK and electrophoretic pattern persisted during her 11-day hospital course. The QuiCK-MB (International Immunoassay Labs.) and Tandem-E CK-MB (Hybritech) immunoassays, however, showed CK-MB mass measurements within the normal range. In further investigation with a mixture of patient's serum and human-serum-based control containing all CK isoenzymes, the electrophoretic mobility of only CK-BB was altered, proving that the patient had antibody to the B unit of CK in her serum. Immunofixation revealed the more anodal band to be a CK-IgA lambda complex, and the more cathodal band, a CK-IgG kappa complex. Mixing the patient's serum with polyclonal antibody specific for CK-B slowed the electrophoretic mobility of only the more anodal band. Polyclonal antibody specific for CK-M had no effect on either band. Evidently, this patient had two different types of macro CK type 1, both containing CK-BB. We conclude that macro CK type 1 can mimic CK-MB and be a source of confusion.

Aged↗

Abdominopelvic computed tomography: evaluation in patients undergoing second-look laparotomy for ovarian carcinoma.

Preoperative abdominopelvic computed tomography results and operative findings were compared in 52 patients undergoing second-look laparotomy to confirm tumor status. Seventeen true-negative, 22 false-negative, and 13 true-positive scans were found. The sensitivity was 0.38, specificity was 1.0, and diagnostic accuracy was 0.58. Negative studies were associated with positive findings at laparotomy in 42% of all cases. Fourteen patients were identified who had computed tomography that would have enabled an attempt at the diagnosis of persistent cancer by computed tomography-directed needle aspiration or biopsy, thus avoiding laparotomy. Assuming 80% accuracy of needle aspiration, the cost of computed tomography in all 52 patients is considerably outweighed by the savings that could have been realized by eliminating the need for second-look surgery in these 11 women.

Antineoplastic Agents↗

Testicular function following combination chemotherapy with cis-platin, vinblastine, and bleomycin.

Recovery of the pituitary-gonadal axis following treatment with vinblastine, bleomycin, cis-platin +/- doxorubicin (VBP +/- A) is assessed retrospectively in 18 men with germinal neoplasms. One patient also received VP-16-213. In the first year after completing treatment all men demonstrated elevated follicle stimulating hormone (FSH) and luteinizing hormone (LH) values with concomitant azoospermia. Of the 11 men evaluated at least 24 months from completion of therapy, seven (64%) had recovery of both FSH and LH to normal or near normal levels. Spermatogenesis was present in five of six (83%) men providing semen samples and who were at least 2 years from stopping VBP. Five of seven (71%) men who were within 24 months of therapy were azoospermic. Regardless of the time of evaluation, most men (94%) had normal serum testosterone. Patients receiving maintenance vinblastine had more prolonged elevation of serum gonadotropins. We conclude that some men have evidence of recovery of fertility beginning two years after VBP +/- A. In addition to germinal epithelium destruction, transient Leydig cell dysfunction occurs but is not accompanied by clinical findings of hypogonadism.

Adolescent↗

The feasibility of adjuvant surgery in limited-stage small cell carcinoma: a prospective evaluation.

Forty patients with limited-stage small cell carcinoma of the lung were prospectively evaluated for adjuvant surgery after intensive chemotherapy to determine resectability. All patients giving informed consent and having a Karnofsky performance status greater than or equal to 50% were included in the study, which ran from May, 1980, to September, 1982. Ages ranged from 40 to 70 years (median, 59 years). One patient was lost to follow-up. Thirty-nine patients were evaluated for operation 9 to 15 weeks after diagnosis and after having received two to four cycles of chemotherapy intravenously every 3 weeks (cyclophosphamide, 1,000 mg/m2; doxorubicin, 50 mg/m2; vincristine, 1 mg/m2; VP-16, 300 mg/m2). Two patients had clinical Stage I tumors; 12 patients, Stage II; and 25 patients, Stage III. At the time of reevaluation there were 13 (33%) complete responders, 21 (54%) partial responders, and 5 (13%) with stable disease. Eleven (28%) of the 39 patients underwent thoracotomy using standard resection criteria for non-small cell carcinoma. Eight of these 11 had resectable lesions (2, Stage I; 3, Stage II; 3, Stage III); five pneumonectomies and three lobectomies were performed. Tumor was present in six of eight specimens. Twenty-eight patients were not candidates for operation for various reasons: poor pulmonary function, 5; unresectable tumors, 10; refusal, 6; very poor medical condition, 6; and primary site not identified, 1. Median survival for complete responders was 17 months and for partial responders, 11 months. We have prospectively identified suitable candidates for adjuvant surgery among the total group (denominator population) of patients with limited-stage small cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report.

A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4,000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completely evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had a complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation (P = .05). In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks (P = .12). Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P = .06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax. Disease-free survival is enhanced in the patients receiving thoracic irradiation. More effective chemotherapy is critically needed to significantly improve overall survival. These preliminary results suggest that thoracic irradiation should be a primary component in the therapy of these patients, although this combined therapy is moderately toxic.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

High-dose VP-16-213 monotherapy for refractory germinal malignancies: a phase II study.

VP-16-213 at standard dose is one of the more active agents for the treatment of germ cell tumors. In previous phase I studies, VP-16-213 has been investigated in suprastandard dose when hematopoietic reconstitution was assured by autologous bone marrow transplantation (ABMT). This phase II study was performed to explore the possibility that an augmented dose of VP-16-213 may be more active than standard dose against germ cell tumors. Eleven patients with progressive refractory germ cell tumors were treated with high-dose VP-16-213: 2,400 mg/m2 with ABMT every three to four weeks followed by 1,200 mg/m2 without ABMT. Seven patients had received VP-16-213 at standard dose prior to high-dose VP-16-213. Toxicity to high-dose VP-16-213 included severe myelosuppression, nausea, vomiting, alopecia, mucositis, and hepatitis. Of 10 evaluable patients, two complete responses and four partial responses, all of short duration, were obtained. However, some patients unresponsive to standard-dose VP-16-213 exhibited responses to the augmented-dose VP-16-213. Therefore, although more myelosuppressive, VP-16-213 may have increased activity against germ cell tumors when administered at augmented dose. High-dose VP-16-213 may be considered in designing new approaches for initial management of patients with germ cell tumors not expected to be cured with standard chemotherapy.

Adolescent↗

Potential utility of serum neuron-specific enolase levels in small cell carcinoma of the lung.

To assess the value of neuron-specific enolase (NSE) as a possible biomarker of small cell lung cancer, serum levels were determined by radioimmunoassay in 93 newly diagnosed untreated patients and were compared to the NSE levels of 20 healthy adult controls [9.6 +/- 0.7 (S.E.) ng/ml]. Serum NSE was elevated (greater than 20 ng/ml) in 73% of all patients including 23 of 39 (59%) with limited-stage disease and 45 of 54 (83%) with extensive-stage disease. The mean serum NSE was significantly higher in extensive-stage disease (94.5 +/- 13.8 ng/ml) compared to the mean value for limited-stage disease (33.7 +/- 4.7 ng/ml) (p less than 0.001). NSE was elevated in all patients with three or more sites of metastatic disease. Serial NSE determinations were obtained on 57 small cell lung cancer patients. NSE levels fell in 40 of 50 (80%) of patients responding to treatment, increased in 5 of 7 (71%) of patients with progressive disease, and increased in 30 of 35 (86%) of patients who relapsed. A persistent rise in serum NSE occurred as many as 12 weeks before the clinical recognition of relapse in 15 of 23 (65%) of patients for whom adequate serial NSE data were available. These findings indicate that serum NSE may be a useful marker for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer.

Carcinoma, Small Cell↗