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Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 181 records · Page 10Linked to original sources

Postchemotherapy resection of residual tumor in limited stage small cell lung cancer.

To determine the feasibility of post-chemotherapy resection of residual tumor in small cell lung cancer, 24 selected patients with limited-stage disease were evaluated for exploratory thoracotomy. All 24 patients achieved partial or complete clinical response to chemotherapy and were considered adequate medical candidates for surgical resection. Fifteen patients underwent a lobectomy or pneumonectomy, 13 of whom had residual tumor in the resected specimen. Of the nine remaining patients, seven had no tumor found on biopsy at thoracotomy and two had unresectable mediastinal node involvement. No chemotherapy was administered postoperatively in any patient until disease progression or relapse was documented. Median survival for the entire group was 19 months and did not differ according to the surgical procedure performed. Nineteen patients had relapse. Patients undergoing biopsy only recurred locally in six of seven cases a median of five months post-thoracotomy (range one to six months). Two "biopsy only" patients were tumor free at 34+ and 56+ months. Local recurrence was observed in six of 12 resected patients, while six patients experienced only extrathoracic metastases. Median time to recurrence for resected patients was also five months. Four resected patients experienced late recurrence 16 to 36 months postoperatively and were alive with tumor at 29+ to 42+ months. Two resected patients were tumor-free at 13+ and 37+ months. Post-chemotherapy surgical resection was feasible in limited-stage patients and improved local control of disease.

Antineoplastic Agents↗

Favorable prognosis of brain metastases in small cell lung cancer.

Brain metastases are found at diagnosis in 10% of patients with small cell lung cancer. To clarify the effect of central nervous system metastases on prognosis, the records of 429 patients with small cell lung cancer were reviewed. Forty-three patients (10%) presented with brain metastases. In 18 patients the brain was the only site of metastatic disease, whereas the remaining 25 patients had at least one additional metastatic site. Forty-one of forty-three patients were treated with combination chemotherapy and cranial radiotherapy. Systemic response rates were similar for both groups. Twenty-seven patients underwent repeat central nervous system staging: 19 (70%) had a complete response, 4 (15%) a partial response, and 4 (15%) no response. Median survival of patients with only one site of metastatic disease was 11 months; patients with additional sites lived 5 months (p = 0.153). Survival in patients with only one site is similar to that in patients with limited disease (11 compared with 13 months; p = 0.074).

Aged↗

Maintenance etidronate in the prevention of malignancy-associated hypercalcemia.

Normocalcemic patients with cancer who had been successfully treated for an episode of hypercalcemia were enrolled in a randomized, multisite, double-blind, placebo-controlled trial designed to determine the efficacy of maintenance oral etidronate in preventing the recurrence of moderate to severe hypercalcemia (serum calcium level, greater than 11.5 mg/dL [greater than 2.87 mmol/L]). Ten (40%) of 25 etidronate-treated patients and 17 (46%) of 37 placebo-treated patients had recurrence of hypercalcemia within 150 days. Although patients taking etidronate had a longer time to the development of hypercalcemia (median, 55 days vs 28 days), this was not significantly different from the control group. The high attrition rate in this trial from hypercalcemia and other malignancy-related causes represents a major difficulty in conducting studies with agents that may require prolonged administration before producing a therapeutic effect.

Administration, Oral↗

Treatment of metastatic adrenal cortical carcinoma with cisplatin and etoposide (VP-16).

Two patients with metastatic adrenal cortical carcinoma were treated with cisplatin and etoposide. Both achieved a partial remission after only one cycle. One patient had a "nonfunctioning" tumor that had previously regressed on mitotane whereas the second patient presented with classical Cushing's syndrome. Although the latter patient's urinary 17-ketosteroids normalized while receiving mitotane, the tumor itself failed to regress objectively. Cisplatin plus etoposide appears to be an active combination for the treatment of metastatic adrenal cortical carcinoma.

Adrenal Cortex Neoplasms↗

Breast cancer with skeletal metastases at initial diagnosis. Distinctive clinical characteristics and favorable prognosis.

Fifteen patients with breast cancer who had skeletal metastases already present at the time the primary breast lesion was detected, were retrospectively identified. The majority were postmenopausal, estrogen receptor-positive, and had large (often neglected) primary lesions. Eleven patients were asymptomatic with respect to their skeletal metastases, although bone scans and bone roentgenograms revealed multiple areas of involvement in all patients. The median survival from the time of diagnosis was 33 months (range, 1-74 months); the 5-year actuarial survival was 45%. Systemic therapy with hormones or chemotherapy was effective in producing subjective responses; radiotherapy to painful bony areas was also an effective palliative treatment. Median survival in this group of patients was significantly improved when compared to our breast cancer patients who had extraskeletal metastases at initial diagnosis (33 versus 9 months, respectively), and to previously reported series of breast cancer patients with metastases at initial diagnosis. Since patients with Stage IV breast cancer and metastases limited to the skeleton often have prolonged survival, complications from bone metastases (e.g. pathologic fracture, epidural spinal cord compression) and other intercurrent illnesses should be managed aggressively.

Actuarial Analysis↗

Phase I study of MVE-2 evaluating toxicity and biologic response modification capability.

A total of 21 patients were treated in a phase I trial using the biological response modifier MVE-2, a low molecular weight component of pyran copolymer. All patients received weekly IV MVE-2 infused over 2 h. Proteinuria, sometimes of nephrotic proportions, was the dose limiting toxicity, and was seen with increasing incidence as the cumulative dose of MVE-2 exceeded 2500 mg. Other toxicity with MVE-2 was minimal. Biologic response modification at tolerable doses was inconsistent, although several assays, particularly natural cell-mediated cytotoxicity, indicated enhanced activity at higher dosages of MVE-2. No objective tumor responses were observed. MVE-2 is not useful as a biological response modifier using our initial method of administration, since the dose limiting toxicity occurred at lower levels than were necessary to induce consistent biologic response modification. Following completion of the phase I study, we administered MVE-2 by 30-min infusion to 8 additional patients and did not detect proteinuria, in spite of large cumulative doses. It is possible that alternate schedules of MVE-2 administration could minimize proteinuria and allow the administration of dosages necessary for immunologic modification.

Adjuvants, Immunologic↗

Lymphocyte-depleted Hodgkin's disease. Clinicopathologic review of 25 patients.

Clinicopathologic material from 25 patients with lymphocyte-depleted Hodgkin's disease was reviewed. The median age of the patients was 57 years. The patients had no prior diagnosis of Hodgkin's disease and were divided according to pathologic subtype of lymphocyte-depleted Hodgkin's disease: 11 diffuse fibrosis, 10 reticular, and four not otherwise specified. The clinical presentation included B symptoms of fever, weight loss, or night sweats (92 percent), subdiaphragmatic disease (88 percent), frequent marrow involvement (56 percent), and advanced-stage disease (100 percent). Four of 11 patients with diffuse fibrosis had peripheral adenopathy as compared with seven of 10 patients with the reticular subtype (p = 0.3); 10 of 11 patients with diffuse fibrosis had marrow involvement compared with two of nine patients with the reticular subtype (p = 0.006). Among patients who received chemotherapy, median survival was longer in the diffuse fibrosis subtype (nine patients, 39 months) than in the reticular subtype (10 patients, 10 months), p = 0.005. Of the 17 patients who received more than one cycle of combination chemotherapy with mechlorethiamine, vincristine, procarbazine, and prednisone, the median survival was 36 months with 11 (65 percent) complete remissions. In eight patients, disease remains in remission (12 to 127 months) with five patients surviving beyond five years. These results indicate that lymphocyte-depleted Hodgkin's disease has at least two clinicopathologic subtypes and is curable if adequate therapy can be given.

Adult↗

Metastatic breast cancer confined to the skeletal system. An indolent disease.

The records of 86 patients with metastatic breast cancer confined to the skeletal system were retrospectively reviewed to evaluate the clinical impression that this subset of patients with metastatic breast cancer has a favorable prognosis. The median survival for this group of patients was 48 months, compared with a median survival of 17 months in patients with breast cancer metastatic to other sites (p less than 0.01). Systemic treatment with either hormonal therapy or chemotherapy was highly effective in these patients; 56 of 64 (87 percent) showed response to the first hormonal therapy received (median, 10 months; range, four to 54 months), and 43 of 46 (93 percent) showed response to initial chemotherapy (median, 11 months; range, six to 22 months). Most patients received several therapeutic modalities sequentially; sequential responses to hormonal therapy were frequent. Orthopedic complications were common (pathologic fracture in 18; epidural spinal cord compression in 13) and occurred a median of 24 months after documentation of bone metastasis. Prolonged survival was common after these complications (median, 18 months; range, two to 48 months). The presence of metastatic disease at the time of diagnosis and premenopausal status were not adverse prognostic factors. Metastases often remained localized to the skeleton; however, appearance of extraskeletal metastasis was associated with short subsequent survival (median, nine months). Metastatic breast cancer confined to the skeletal system is a common entity that can be defined clinically, is highly responsive to treatment, and is frequently associated with prolonged survival.

Adult↗

Acute nonlymphocytic leukemia after treatment of small cell lung cancer.

From 1977 to 1982, 377 patients with small cell lung cancer were treated at Vanderbilt University Medical Center. All patients received combination chemotherapy consisting of cyclophosphamide, doxorubicin, and vincristine (CAV) with or without methotrexate, etoposide, and/or hexamethylmelamine. Thoracic and/or prophylactic cranial irradiation was administered to 159 (42 percent) and 192 (51 percent) patients, respectively. Acute nonlymphocytic leukemia was observed in two patients at 22 and 81 months from the start of therapy. The relative risk of leukemia was 154 (95 percent confidence limit, 38 to 293). A Kaplan-Meier estimate of the cumulative probability of leukemia was 1.9 +/- 1.4 percent seven years after the start of treatment. The relative risk of leukemia is significantly increased in this group of patients (p less than 0.0001). Acute nonlymphocytic leukemia is a long-term complication of small cell lung cancer therapy.

Adult↗

Malignant mixed mesodermal tumors of the uterus and ovary treated with cisplatin-based combination chemotherapy.

Twelve patients with malignant mixed mullerian tumors were treated with combination chemotherapy at Vanderbilt University Hospital from 1977 through 1981. Nine patients, all of whom received combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (HCAP), were evaluable for response. Objective responses (all partial responses) were noted in 3 (33.3%) (response rate greater than 10% and less than 55% with 90% confidence limits), a minimal response was noted in one patient, and stable disease in four (50%) patients. Responders survived longer (calculated from the initiation of HCAP) than nonresponders (median 112 vs 19 weeks). These results are not at present statistically different from previous studies utilizing doxorubicin alone, cisplatin alone, the combination of doxorubicin and DTIC, or the combination of vincristine, actinomycin D, and cyclophosphamide.

Aged↗

Small cell carcinoma of the lung.

Small cell lung cancer is a common, usually fatal neoplasm. Although palliative therapy is available for the majority of patients, only a very small minority enjoy long-term survival. Ironically, this neoplasm is nearly entirely preventable and a successful antismoking program is desperately needed. Our efforts to understand the basic biology of this tumor should continue, and, hopefully, will eventually translate into improvements in therapy. In addition to following the leads provided by basic research, a concerted clinical research effort needs to continue to build upon the advances already achieved.

Antineoplastic Agents↗

Phase I-II evaluation of razoxane (ICRF-159) and doxorubicin in gastrointestinal cancer. A Southeastern Cancer Study Group Trial.

A Phase I-II study of razoxane (ICRF-159) and doxorubicin was undertaken in 34 adults with advanced gastrointestinal carcinoma. Three dose schedules were studied; weekly razoxane at 600 mg/m2 orally plus doxorubicin 60 mg/m2 every 3 weeks, razoxane at 300 mg/m2 plus doxorubicin 60 mg/m2, and weekly razoxane 300 mg/m2 plus doxorubicin 35 mg/m2 every 3 weeks. This combination produced moderate to severe granulocytopenia in 24 patients including granulocytopenia less than or equal to 500/mm3 in 15. The granulocytopenia occurred regardless of prior chemotherapy and regardless of dose schedule employed. Two septic deaths were recorded but no responses. Further evaluation of this combination is not recommended.

Adenocarcinoma↗

Combination intraventricular chemotherapy for meningeal neoplasia.

Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Antiemetic effect of oral versus intravenous metoclopramide in patients receiving cisplatin: a randomized, double-blind trial.

In a study of the antiemetic effectiveness of high-dose oral metoclopramide, 66 previously untreated patients receiving 60 mg/m2 cisplatin were entered into a double-blind randomized trial. Patients were stratified according to age and tumor type, then randomized to receive either oral or intravenous (IV) high-dose metoclopramide. Patients were evaluated for antiemetic protection, toxicity, affect (anxiety, hostility, and depression), and autonomic arousal (pulse rate and blood pressure) at three-hour intervals on the day of their chemotherapy. Metoclopramide serum levels were measured by high-performance liquid chromatography. Results indicated no significant differences between the oral and IV groups on any measurement of antiemetic protection, affect, or autonomic arousal. There were also no significant differences in side effects except for frequency of stools; patients who received oral metoclopramide had significantly more stools than patients who received IV metoclopramide. The mean (+/- SD) serum metoclopramide level at four hours achieved orally was 1,171 +/- 660 ng/mL; the mean (+/- SD) level achieved IV was 1,030 +/- 392 ng/mL (P = .498). We conclude that high-dose oral and IV regimens of metoclopramide as administered in this study have equivalent antiemetic efficacy in previously untreated patients receiving 60 mg/m2 cisplatin.

Administration, Oral↗

Prognostic factors for favorable outcome in disseminated germ cell tumors.

Between 1978 and 1982, 180 patients from Indiana University (Indianapolis) were entered on the Southeastern Cancer Study Group (SECSG) protocol 78 GU 240, a randomized comparison of cisplatin, vinblastine, and bleomycin (PVB) v PVB plus doxorubicin induction chemotherapy regimens, with a second randomization to maintenance vinblastine v no further therapy. One hundred forty-eight of these patients obtained a favorable response to chemotherapy, defined as a complete response (CR) or a surgical resection of teratoma. The prognostic significance of various patient characteristics was investigated using the logistic regression model. Two classifications for the extent of disease were considered: the Indiana staging system and the M.D. Anderson (MDA) staging system. The Indiana staging system had the greater prognostic significance. This staging system allowed the population to be split into three groups (minimal, moderate, advanced disease) in which the observed proportions of favorable responders were 99%, 90%, and 58%, respectively. Within the advanced group, the number of elevated tumor markers subdivided these patients into three groups, with the observed proportions of favorable responders being 73%, 65%, and 45%. The Indiana and MDA staging systems were subsequently prospectively used in SECSG protocol GU 81 332, a study randomizing patients to remission induction therapy with PVB v cisplatin, VP-16, and bleomycin. The prognostic value of the Indiana staging system was prospectively validated in this study.

Adolescent↗