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Biomedical subjects

P Bonomi

Publications and source records attributed to P Bonomi.

At least 73 records · Page 4Linked to original sources

Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma.

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.

Adenocarcinoma↗

Phase I trial of cisplatin and razoxane (ICRF-159) (NSC #119875) in advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Pilot Study.

Both cisplatin and razoxane have shown activity in squamous carcinoma of the cervix. Cisplatin at a dose of 50 mg/m2 intravenously every 21 days was combined with razoxane at two dose levels--750 mg/m2 weekly and 1150 mg/m2 weekly. Three patients were treated at the first dose level and six patients were treated at the second dose level of razoxane. No objective regressions were observed, and three patients refused to continue therapy at the higher dose of razoxane because of nausea and vomiting. Further study of this regimen in cervical cancer is not recommended.

Adult↗

Continuous infusion of etoposide, bolus administration of cisplatin, and simultaneous radiation therapy in previously treated patients with small cell bronchogenic carcinoma.

Thirty-one patients with previously treated small cell bronchogenic carcinoma were treated with split-course radiation therapy and concurrent cisplatin and etoposide. Twenty-four patients (78%) had clinical partial or complete responses. Median survival from the time of salvage was 6.3 months. Fifty-eight percent of the patients failed on therapy initially in sites outside the radiation port. Hematologic toxicity was moderate. Concurrent cisplatin, etoposide, and split-course radiation therapy is feasible and active in the treatment of small cell bronchogenic carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Concomitant therapy with infusion of cisplatin and 5-fluorouracil plus radiation in stage III non-small cell lung cancer.

Based on our experience with head and neck cancer, we have developed an every-other-week, split-course schedule for giving combined cisplatin and 5-fluorouracil infusion and radiation to patients with regionally advanced non-small cell lung cancer for a limited number of cycles prior to planned resection. Sixty-four patients having stage III disease without distant metastases were treated with 4 cycles of combined chemotherapy and radiation to 40 Gy and were offered surgical resection. Thirty-nine patients (61%) underwent surgery. Nine had no residual cancer. No correlation was noted between clinical and histologic responses in the surgery group, but histologic response correlated with subsequent outcome. Survival was 58% at 1 year, 33% at 2 years, and 22% at 3 years. Although encouraging, the overall dismal prognosis of this disease has led us to pursue further improvements in protocol design prior to phase III testing of this concept. To this end, etoposide has been added to the above regimen, extending the cycles from every other week to every third week.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II trial of therapy with etoposide, 5-fluorouracil by continuous infusion, cisplatin, and simultaneous split-course radiation in stage III non-small cell bronchogenic carcinoma.

Survival of patients who have clinical stage IIIM0 non-small cell bronchogenic carcinoma remains relatively short despite treatment with either surgery or radiation. Results from a phase II study of simultaneous continuous infusion of 5-fluorouracil, cisplatin, and split-course radiation with or without surgery indicate that median survival duration in patients treated with this combined modality approach may be better than the median survival for patients treated with radiation alone. Etoposide has been added to this regimen, and 32 stage IIIM0 non-small cell lung cancer patients have been treated with the 3-drug regimen resulting in a 73% clinical partial remission rate. No residual tumor was found in 6 of 12 patients who had pulmonary resection after 4 courses of chemotherapy and radiation. The sites of failure in 8 patients with recurrent disease are as follows: local only, 3; distant only, 4; and local and distant, 1. The major toxicities have been leukopenia, nausea, and vomiting. The median leukocyte nadir was 2,400/mm3. A leukocyte count less than 1,000/mm3 was observed in 2 patients (7%), 1 of whom died of progressive pneumonia. All patients experienced nausea, vomiting, and anorexia. Severe esophagitis, dermatitis, and pneumonitis were not observed. Survival analysis has not been done because median follow-up time (326 days) is relatively short.

Antineoplastic Combined Chemotherapy Protocols↗

Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation.

Neuroendocrine carcinomas were diagnosed in 13 of 683 patients who had colon cancers removed from January 1980 to June 1987 for an incidence of 1.9%. The patients were 28 to 89 years of age (median, 72 years). There were seven male and six female patients. The treatment was as follows: right hemicolectomy, 5; transverse colectomy, 1; left hemicolectomy, 1; low anterior resection, 2; abdominal-perineal resection, 1; and in 3 patients with rectal tumors, biopsy examination only was performed. Microscopic stages were as follows: Dukes' stage B, 1; stage C, 6; stage D, 5; and stage indeterminate, 1. By light microscopy, the tumors showed solid clusters or ribbons of round to fusiform, small to intermediate-sized cells with variably abundant mitoses. Eight tumors had foci of glandular and/or squamous differentiation. By immunohistochemistry, all tumors showed one or more neuroendocrine markers, including neuron-specific enolase, chromogranin, synaptophysin, serotonin, and various neuropeptides. By electron microscopy, single membrane-bound neurosecretory granules were noted. The sites of metastases included regional nodes, 8; liver, 5; bone, 1. Four patients were treated with a combination of chemotherapy and radiation therapy. These tumors were, as a group, aggressive, with eight patients dead within 12 months of diagnosis. Median survival was 7 months, with three patients alive at 2, 38, and 68 months, respectively. Specifically, small- and intermediate-cell neuroendocrine carcinomas of the colon and rectum behaved very aggressively and displayed numerous structural and functional similarities with their bronchopulmonary counterparts.

Adult↗

Quantitative estrogen and progesterone receptor levels related to progression-free interval in advanced breast cancer patients treated with megestrol acetate or tamoxifen.

Estrogen receptor (ER) and progesterone receptor (PgR) levels have been reported to have prognostic significance with respect to disease-free survival in early-stage breast cancer patients. The current retrospective study was undertaken to determine whether ER and PgR levels, as well as other potential prognostic factors, might be related to a progression-free interval (PFI) during additive hormonal therapy in advanced-stage breast cancer patients. Eligibility requirements for this study included the following: histologically confirmed recurrent or metastatic breast cancer, known quantitative ER and PgR levels, postmenopausal status, treatment with either megestrol acetate or tamoxifen, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. The characteristics of the 105 patients included in these analyses were as follows: median age, 62 years; median disease-free interval (DFI), 523 days; median ER level, 44 fmol/mg; median PgR level, 52 fmol/mg; soft tissue-dominant disease, 37 patients (35%); bone-dominant disease, 36 patients (34%); visceral-dominant disease, 32 patients (31%); one site of disease, 60 patients (58%); two or more sites of disease, 45 patients (42%); treatment with megestrol acetate, 62 patients (59%); treatment with tamoxifen, 43 patients (41%). All of the independent variables listed immediately above were included in a multiple linear regression analysis in which PFI, expressed as log PFI, was the dependent variable. In this analysis, a positive linear relationship was observed between log PFI and the following independent variables: log ER, log PgR, and age (r2 = 0.329). An alternative model (r2 = 0.350) was derived, in which previous treatment with chemotherapy was negatively related to log PFI. However, it appears that previous treatment with chemotherapy could be a "proxy variable," because patients who had been treated with chemotherapy previously were significantly younger and had significantly lower ER (P = 0.0001) and PgR levels (P = 0.0004). None of the other independent variables were included in these models. If the assumption that PFI is a measure of the effectiveness of hormonal therapy is true, these results suggest that quantitative ER and PgR levels and age supersede other traditional predictor variables in predicting the hormonal responsiveness of individual breast carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Megestrol acetate as primary hormonal therapy for advanced breast cancer.

The records of 133 patients treated with megestrol acetate as primary hormonal therapy for advanced breast cancer were reviewed retrospectively, using International Union Against Cancer (UICC) criteria for response. The median age was 65 years, 121 patients were over age 50, and the age range was 39 to 94 years. Response rates (complete response [CR] + partial response [PR]/total) by qualitative receptor level, with levels of 10 fmol/mg of protein considered positive, were as follows (ER = estrogen receptor, PgR = progesterone receptor): For ER + PgR+, 13 + 15/56 (50%); for those with one positive receptor, 0 + 12/47 (26%); for ER - PgR-, 0 + 0/12 (0%); and for receptor-unknown cases, 2 + 3/18 (14%). Response for ER less than 30 fmol/mg was 2 + 6/39 (21%); for ER 30 to 50, 1 + 5/16 (40%); and for ER greater than 50 fmol/mg, 11 + 15/56 (46%). For PgR less than 30, response was 0 + 6/37 (16%); for PgR 30 to 50 fmol/mg, 1 + 4/14 (36%); and for PgR greater than 50 fmol/mg, 12 + 13/54 (46%). For the 75 patients with a disease-free interval (DFI) of 2 years or less, the response rate was 5 + 1/75 (8%), and for the 58 patients with DFI greater than 2 years, 10 + 12/60 (37%). For patients with prior chemotherapy, 3 + 8/49 (22%) had an objective response. For those with no prior chemotherapy, 12 + 19/84 (37%) responded. Response by dominant site of disease was as follows: soft tissue 12 + 9/43 (49%), bone 2 + 13/49 (31%), viscera 2 + 5/41 (17%). Of these seven patients with visceral dominant disease who responded, all had PgR levels greater than 50 fmol/mg, all but one had an ER level over 100 fmol/mg, all but one were over age 65, and all but two received no prior chemotherapy. We conclude that megestrol acetate is effective initial hormonal therapy for patients with advanced breast cancer. It may have some role to play in the treatment of carefully selected cases with visceral disease.

Adult↗

Megestrol acetate v tamoxifen in advanced breast cancer: correlation of hormone receptors and response.

This report describes the preliminary results from a randomized study comparing megestrol acetate with tamoxifen in the treatment of postmenopausal women with advanced breast cancer, correlating estrogen receptors (ER) and progesterone receptor (PgR) status with response. Patients received megestrol acetate (40 mg) orally four times daily or tamoxifen (10 mg) orally twice daily. If the initial therapy failed, patients were crossed over to the alternate treatment. Of 197 patients entered in the study, 190 were considered evaluable. The overall response rates were 35% with megestrol acetate and 42% with tamoxifen. Twenty-three percent (7/30) of patients responded to megestrol acetate after being crossed over from tamoxifen, while 22% (6/27) responded to tamoxifen after being crossed over from megestrol acetate. Response did not correlate significantly with combined receptor (ie, ER plus PgR) levels. A significant trend was seen between ER level and response only in the tamoxifen group. There was no association between PgR levels and response for either tamoxifen or megestrol acetate.

Antineoplastic Agents↗

Phase II trial of etoposide, cisplatin, continuous infusion 5-fluorouracil, and simultaneous split-course radiation therapy in stage III non-small-cell bronchogenic carcinoma.

Survival in patients with locally advanced, non-small-cell lung cancer (NSCLC) is relatively short, despite treatment with surgery or radiation. A phase II study of simultaneous continuous infusion 5-fluorouracil and split-course radiation with or without surgery has shown possible improvement in median survival compared with that observed in trials of radiation alone. Past success with etoposide plus cisplatin in NSCLC has led to the addition of etoposide to the 5-fluorouracil plus cisplatin plus radiation combination. Twenty-four stage III NSCLC patients were treated with this three-drug regimen, and a 74% clinical partial remission rate was observed. Thoracotomy was done in eight of these patients; subsequent histologic examination of the resected specimen revealed no residual tumor in four patients (50%) and only microscopic foci of tumor in two patients (25%). Major toxicities were leukopenia, nausea, and vomiting. Median leukocyte nadir was 2,900/mm3. A leukocyte count less than 1,000/mm3 was observed in two of 24 patients (8%), one of whom expired from progressive pneumonia. All patients experienced nausea and vomiting, which were classified as moderate in three patients (12%) and severe in four (16%). Moderate to severe esophagitis, dermatitis, and pneumonitis were not observed. Median progression-free interval and median survival were not reached after a median follow-up of 163 days.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of soft tissue sarcoma with fibroblast interferon (beta-interferon): an American Cancer Society/Illinois Cancer Council Study.

Twenty patients with soft tissue sarcoma were treated with iv human fibroblast interferon (beta-interferon). Each cycle of treatment involved 5 X 10(6) units over 10 minutes, then 5 X 10(6) units iv over 3 hours daily X 10 with cycles repeated every 20 days X 3. Maintenance therapy was given twice weekly if disease was stable or responsive after three therapy periods. One patient had a partial response to treatment and six patients experienced stable disease for variable periods of time. Toxicity (fever, fatigue, leukopenia, hepatic enzyme elevations) was moderate and tolerable; therapy (except in one case of profound granulocytopenia) was neither interrupted nor discontinued because of toxicity. We conclude that beta-interferon in the dose and schedule used has limited value for soft tissue sarcoma.

Adult↗

Qualitative analysis of Coomassie-blue-stained proteins from normal prostate, benign prostatic hypertrophy, or adenocarcinoma of the prostate, separated by two-dimensional protein electrophoresis.

Samples from nine normal prostates (N), ten benign hypertrophic prostates (BPH), and eight adenocarcinomas of the prostate (ACP), obtained from the National Prostatic Cancer Project were analyzed by two-dimensional (2D)-protein electrophoresis. Qualitative analysis of Coomassie-blue-stained acidic proteins between pI 3.5 and 6.8 yielded these results: The total number of enumerated proteins was 136 (N), 107 (BPH), and 147 (ACP). Ninety-two denoted proteins were deemed common to the three kinds of samples, three were considered present in N and BPH, 7 in BPH and ACP, and 28 in N and ACP. Thirteen, five, and 20 proteins were detected only in N, BPH, or ACP. These proteins cannot be considered "unique" to their respective samples, since amounts of protein that do not exceed the minimum sensitivity of the dye may be present in the other samples. The similarity in the patterns of proteins from these three types of prostate samples is consistent with the following hypothesis: The distribution of proteins from histologically ambiguous prostate samples will correlate more closely with these protein profiles than with those associated with cancers originating from other organs.

Adenocarcinoma↗

Progestin therapy for breast cancer: a panel discussion.

The use of pharmacologic doses of steroid hormones to treat patients with advanced breast cancer has been standard for many years. Recently there has been increased interest in the investigation of progestational agents, largely as a result of their excellent response rate in selected patients and their minimal side effects. In this panel discussion the participants discuss the use of progestin in advanced and early breast cancer. Criteria for patient selection, such as receptor status or response to previous therapies, are analyzed, and dose-response relationship and the side effects are addressed.

Breast Neoplasms↗

Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study.

The Gynecologic Oncology Group has conducted a randomized prospective trial comparing cisplatin 50 mg/m2 every 21 days (regimen 1), 100 mg/m2 every 21 days (regimen 2), and cisplatin 20 mg/m2 for five consecutive days repeated every 21 days (regimen 3). Four hundred ninety-seven evaluable patients have been accrued on this study. The response rates were 20.7%, 31.4%, and 25.0%, for regimens 1, 2, and 3, respectively; the complete remission rates were 10.0%, 12.7%, and 8.6% for regimens 1, 2, and 3, respectively. The median duration of response ranged from 3.9 to 4.8 months, the median progression-free interval from 3.7 to 4.6 months, and the median survival time from 6.1 to 7.1 months. The difference in response rates for regimens 1 and 2 is statistically significant (P = .015) but less than the magnitude originally considered clinically significant. The differences in complete remission rates, response duration, progression-free interval, and survival times are not statistically significant. The following types of toxicity were observed: serum creatinine level greater than 2 mg/dL and/or BUN level greater than 40 mg/dL was 7%, 14%, and 17% on regimens 1, 2, and 3, respectively; leukocyte count less than 4,000/microL was 27%, 44%, and 41% on regimens 1, 2, and 3, respectively. Nausea and vomiting occurred in 74 patients (83%). The regimen consisting of a 100-mg/m2 single dose has produced a statistically significant higher response rate than the 50 mg/m2 regimen while producing no appreciable differences in complete remission rate, response duration, progression-free interval, or survival. In addition, the higher dose regimen was associated with greater myelosuppression and nephrotoxicity.

Adult↗

Remission of invasive thymoma due to chemotherapy. Two patients treated with cyclophosphamide, doxorubicin, and vincristine.

Information regarding the effectiveness of chemotherapy in cases of invasive thymoma is limited. Two patients in whom the combination of cyclophosphamide, doxorubicin, and vincristine produced remission of invasive thymoma are described. The durations of remission were eight and seven months, respectively. In both patients, recurrence was observed at the site of bulky disease, and a secondary complete response continuing for 37 months was achieved in one of them with radiation therapy.

Aged↗

Intensive induction treatment of small cell bronchogenic carcinoma with cyclophosphamide, methotrexate, and etoposide.

Fifty-six patients with histologically confirmed small cell bronchogenic carcinoma were treated with cyclophosphamide, methotrexate, and etoposide. While methotrexate doses were modified for mucositis during the 6-week induction period, none of the drug doses were modified for hematologic toxicity. The overall response rate was 66%, with 16% complete remissions; median survival duration was 28 weeks. In 12 patients, the leukocyte count fell below 1000/mm3, and there were four deaths in febrile, leukopenic patients. Diffuse pulmonary infiltrates were observed in eight patients, and three died from respiratory insufficiency. Lung biopsy in two patients and autopsy in two additional patients showed interstitial changes consistent with drug injury. This regimen produced considerable hematologic and apparent pulmonary toxicity while offering no advantage in response rate or survival duration.

Antineoplastic Combined Chemotherapy Protocols↗

A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial.

A prospective randomized trial of low versus high doses of human leukocyte alpha-interferon (1 X 10(6) units/day for 28 days versus 10 X 10(6) units/day for 28 days) was carried out in 30 patients with metastatic renal cell carcinoma, to test the tolerance and relative antitumor effects of these interferon doses. Both doses were tolerated well, and responses to the human leukocyte alpha-interferon were observed overall in seven individuals, including complete, partial, and minimal tumor regressions. Six of the seven responses occurred in patients who received the high dosage, and three of these responses were major responses. While not statistically significant, this result suggested a dose-response relationship. One minimal response was observed in a patient treated at low dosage. Nine individuals who were stable after 1 month of therapy at low dosage were randomized to a further month of therapy at low or high dosage, during which one of four at high dosage had a partial response, and none of five at low dosage manifested response. Regression of pulmonary disease in one individual was delayed, occurring 3 months after therapy at the high dose and enduring for a period of 28 months. Major objective responses in other patients were of 4 and 15 months duration. Human leukocyte alpha-interferon is an active agent in renal cell carcinoma at the dosage of 10 million units daily. No relationship of toxicity to response was evident in this trial. Optimum dosage and duration of treatment have yet to be established.

Adenocarcinoma↗