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Biomedical subjects

P Bonomi

Publications and source records attributed to P Bonomi.

At least 55 records · Page 3Linked to original sources
PubMed1994

Potential applications of apoptosis in modifying the biological behavior of therapeutically refractory cancers.

Recent information about apoptosis or programmed cell death, the anti-apoptotic gene, BCL2, its interaction with reactive oxygen species and the role of these agents in senescence and apoptosis, suggests a discussion of their relationships could be of interest. Such information may eventually provide alternative approaches to modifying the biological behavior of therapeutically resistant cancers. Some of these comments probably are self-evident, others may be less so and provide ideas for further studies.

Apoptosis↗
PubMed1994

Phase II trial of acivicin versus etoposide-cisplatin in non-small cell lung cancer. An Eastern Cooperative Oncology Group study.

Identification of effective new chemotherapeutic agents is a major objective of clinical research efforts in patients who have metastatic non-small cell lung cancer (NSCLC). Canadian investigators observed responses in NSCLC when acivicin was given as a daily IV bolus for 5 consecutive days. Based on these results the Eastern Cooperative Oncology Group tested acivicin as a continuous infusion in patients with advanced NSCLC. A total of 82 patients were entered on a Phase II trial in which patients have randomized either to acivicin 60 mg/m2 given as a continuous intravenous infusion over 72 hours repeated every 28 days or to the reference regimen which consisted of cisplatin 60 mg/m2 intravenously on day 1 and etoposide 120 mg/m2 daily on days 1, 2, and 3 repeated every 28 days. Five partial remissions (11%) were observed in 42 patients treated with etoposide-cisplatin, and no responses were observed in 40 patients treated with acivicin. Median survival durations for etoposide cisplatin and for acivicin were 29.7 and 21.1 weeks, respectively. Based on these results, acivicin appears to be inactive in NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Alteration of integrated optical density and intercellular structure after induction chemotherapy and survival in lung carcinoma patients treated surgically.

Histologic sections of formalin-fixed, paraffin-embedded tissue consisting of 53 surgical specimens, 48 biopsy specimens and 29 intrapulmonary lymph nodes of human non-small cell lung carcinoma were Feulgen stained. The biopsy specimens were obtained before and the surgical specimens after induction chemotherapy (down staging). The integrated optical density (IOD) of tumor cell nuclei was measured using an automated image analysis system, and the attributed minimum spanning trees (MSTs) were computed. The measured features included IOD (DNA content of the nuclei), IOD entropy, S-phase-related fraction (SRF), percentage of tumor cells with an IOD > 5C (P5C), standard deviation of IOD and structural parameters (minimum distance between neighboring tumor cell nuclei, minimum distance between tumor cell nuclei and neighboring lymphocytes, MST entropy, minimum distance between neighboring proliferating tumor cell nuclei, etc.). The measured IOD and MST features showed significant differences in the biopsy specimens as compared to those measured in the surgically excised carcinomas and those growing in the intrapulmonary lymph nodes (lymph node metastases). After down staging, the SRF was significantly diminished, and the percentage of cells with an IOD > 5C increased (P < .05). The survival of patients was remarkably improved if both the carcinomas before and after induction chemotherapy displayed a low SRF, a low number of stemlines and low MST entropy.

Adenocarcinoma↗
PubMed1994

Treatment of stage III non-small cell lung cancer with thoracic radiation therapy and simultaneous platinum chemotherapy.

Preclinical trials have shown platinum compounds to enhance radiation, and clinical trials that tested simultaneous cisplatin and radiation in a variety of tumors have demonstrated acceptable toxicity. Subsequent reports described the use of platinum chemotherapy and concurrent thoracic radiation therapy for the treatment of locally advanced non-small cell lung cancer. In patients whose disease was considered unresectable, investigators have tested cisplatin primarily as a single agent. Phase III trials compared single-agent cisplatin and simultaneous radiation with radiation alone. Selected phase II trials studied cisplatin, or carboplatin and radiation. Two phase II trials evaluated cisplatin-containing combination chemotherapy and simultaneous split-course radiation therapy in nonsurgical patients. In contrast to nonsurgical trials, studies of preoperative treatment have tested cisplatin-containing combination chemotherapy regimens and simultaneous radiation. Of particular interest are the implications of these studies for future phase III trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Radiation and simultaneous cisplatin in non-small cell lung cancer.

PURPOSE: Phase III non-small cell lung cancer trials comparing radiation and simultaneous single agent cisplatin-radiation, as well as, Phase II trials of cisplatin containing combination regimens and concurrent thoracic radiation used as preoperative or as definitive therapy in stage III non-small cell lung cancer are reviewed. METHODS AND MATERIALS: The prognostic significance of the new international staging system with respect to clinical Stage III disease is described and discussed in this review because it has important implications for clinical trials. The results of four randomized Phase III trials and one Phase II trial which evaluated radiation therapy and single agent cisplatin are reviewed. The data from studies of combination chemotherapy and concurrent thoracic radiation observed in two consecutive Rush University Phase II trials and in a randomized Phase II Mayo Clinic trial are described. Eight phase two studies in which thoracic radiation and simultaneous cisplatin containing combination chemotherapy were given as preoperative treatment are compared. RESULTS: Studies evaluating the prognostic significance of the new staging system (IIIa vs IIIb) have shown conflicting results. In Rush University trials there has been a significant difference for IIIa versus IIIb and in particular the tumors which are invading the mediastinum or chest wall without obvious mediastinal lymph node metastases appear to have the best prognosis. Similarly randomized trials evaluating curative doses of thoracic radiation therapy with or without current single agent cisplatin have shown contradictory results. One of the four randomized trials have shown superior survival with patients treated with radiation and simultaneous daily cisplatin. Toxicity with cisplatin combination chemotherapy regimens and split course radiation has been acceptable. In Phase II non-surgical trials preoperative treatment consisting of cisplatin containing combination regimens given simultaneously with thoracic radiation have shown that this type of combined modality therapy is feasible and that the rates of resectability appear to be higher than would be expected with surgery alone. Survival results from six of these studies appear to be superior to results reported for radiation or surgery alone. CONCLUSION: Additional data are needed to determine the prognostic significance of the new staging system for clinical Stage III non-small cell lung cancer patients. Similarly, additional Phase III trials will be required to determine the role of thoracic radiation and concurrent single agent cisplatin, as well as, concurrent cisplatin combination regimens. Treatment with preoperative radiation and concurrent cisplatin containing combination therapies is feasible and relatively safe. Phase III trials are needed to determine the impact of neoadjuvant chemoradiation therapy and surgery in Stage III patients.

Adult↗
PubMed1993

Alternating chemotherapy and twice-daily thoracic radiotherapy in limited-stage small-cell lung cancer: a pilot study of the Eastern Cooperative Oncology Group.

PURPOSE: This pilot study was undertaken to determine the efficacy and feasibility of alternating cisplatin and etoposide with multiple daily fractions of thoracic radiotherapy (TRT) in patients with limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-four SCLC patients received four courses of cisplatin (30 mg/m2/d x 3) plus etoposide (120 mg/m2/d x 3) (PE) every 3 weeks. TRT was administered twice daily (1.5 Gy per fraction) for 5 consecutive days in the week after cycles 1, 2, and 3 of chemotherapy (total TRT dose, 45 Gy). Patients who achieved a complete response (CR) received one course of late-intensification (LI) treatment consisting of cyclophosphamide (4 g/m2) and etoposide (900 mg/m2). Prophylactic cranial irradiation (PCI) was optional. RESULTS: Nineteen of 32 assessable patients achieved a CR (59%) and 12 had a partial response (38%), for an overall response rate of 97% (95% confidence interval [CI], 84% to 99%). Median survival was 18 months, while 2-year progression-free survival was 47%. Leukopenia < or = 1,000/microL occurred in 12% of induction treatment cycles. Severe esophagitis was uncommon. Pulmonary fibrosis that was asymptomatic or minimally symptomatic was observed in eight patients (25%). There was one episode of adult respiratory distress syndrome (ARDS) during LI chemotherapy. Life-threatening neutropenia (< or = 500/microL) developed in all patients who underwent LI chemotherapy, with a median duration of 10 days (range, 8 to 19). Two patients died of sepsis during LI chemotherapy. CONCLUSION: Alternating PE and TRT as performed in this trial is an effective brief induction regimen for limited-stage SCLC. However, this particular regimen did not appear to be substantially different in terms of efficacy or toxicity compared with regimens using concurrent chemotherapy and standard-fraction TRT. LI chemotherapy was associated with unacceptable toxicity and did not appear to have a favorable impact on survival.

Aged↗
PubMed1992

Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure.

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Platinum/etoposide therapy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a major health problem in the United States and in many other parts of the world. Identification of systemic therapy that can maintain or improve quality of life and prolong survival is essential because locally advanced disease or distant metastasis is found in the majority of these patients. A variety of combination regimens have produced response rates of 20% or greater in stage IV NSCLC patients in cooperative group trials, including studies conducted within the Eastern Cooperative Oncology Group (ECOG). Although no regimen has emerged as clearly superior, the highest 1-year survival rate (25%) in ECOG trials was observed in EP(etoposide/cisplatin)-treated patients. Subsequently, a randomized trial in which EP was compared to etoposide/carboplatin revealed no significant differences in survival or response rate, and toxicity was slightly less with etoposide/carboplatin. Results from recent phase II trials in which stage III NSCLC patients received preoperative EP and concurrent thoracic irradiation have shown response rates of 65-85%, as well as acceptable toxicity and surgical morbidity and mortality. Future stage IV NSCLC trials should include studies of platinum/etoposide plus new agents. Also a study comparing platinum/etoposide versus supportive care should be considered. The objectives of this study would be to compare survival, quality of life, and cost-effectiveness ratio. The results of recent phase II studies in stage III NSCLC patients suggest that preoperative cisplatin/etoposide and concurrent thoracic irradiation should be considered for evaluation in a phase III trial in stage IIIa NSCLC patients and that this regimen should also be evaluated in stage IIIb patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Recent advances in etoposide therapy for non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) continues to be a major health problem in the US. In 1990, approximately 120,000 new cases will be diagnosed, and the majority of these patients will have either unresectable disease or resected disease that has a relatively low chance of being cured. A variety of chemotherapy treatments have been evaluated in patients with advanced NSCLC. The objective of this review is to summarize the results of the chemotherapy trials in Stage III and IV NSCLC patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Pre-treatment prognostic factors in stage III non-small cell lung cancer patients receiving combined modality treatment.

Approximately one-third of non-small cell lung cancer (NSCLC) patients present with locally advanced disease. Increasing numbers of clinical trials are being conducted in this group of patients and recently a new international staging system has been introduced, resulting in the sub-division of Stage III into IIIa (potentially operable disease) and IIIb (inoperable disease). Kaplan-Meier survival analyses and Cox regression analyses were used to analyze data from 129 Stage III NSCLC patients who had been treated on two consecutive Phase II trials testing combined modality treatment. The pretreatment characteristics of these patients were: median age--59 years, males/females--87/42, caucasian/non-caucasian--111/18, squamous cell or adenocarcinoma/large cell carcinoma--57/72, previous weight loss less than or equal to 5%/greater than 5%-76/46, previous history of cardiorespiratory disease--no/yes--91/36, performance status (PS) 0-1/2-3--102/27, Stage III, 2 groups--IIIa/IIIb--83/46, Stage III, 3 groups--IIIa T3 N0/IIIa N2/IIIb--41/41/47, surgical eligibility--eligible/ineligible--83/46. Kaplan-Meier statistics revealed significantly longer survival for PS 0-1 versus 2-3 (p = .001), for eligible versus ineligible for surgery (p = .003), for Stage-IIIa versus IIIb (p = .004), and for Stage-IIIa T3N0 versus IIIa N2 versus IIIb (p = .004). The best model developed from Cox regression analyses included stage (IIIa T3 N0 vs IIIa N2 vs IIIb), PS, and sex. These observations appear to have implications for clinical research in Stage III NSCLC.

Adenocarcinoma↗
PubMed1991

Carboplatin in non-small cell lung cancer: review of the Eastern Cooperative Oncology Group trial and comparison with other carboplatin trials.

Clinical trials evaluating carboplatin as a single agent or as a component of combination regimens in the treatment of non-small cell lung cancer (NSCLC) patients are reviewed in this report. Response rates for carboplatin varied from 9% to 20% in four trials testing carboplatin 400 mg/m2 as a single daily dose or given over 3 days. In one of these trials carboplatin treatment was associated with a modest but significant survival benefit, and in all of the trials severe toxicity was minimal. In a randomized trial comparing carboplatin/etoposide to cisplatin/etoposide, no significant differences were observed in response rates or survival duration, but there was a trend for less toxicity with carboplatin/etoposide. Other investigators have evaluated carboplatin in two-drug combination therapy with vinblastine, cisplatin, or etoposide in phase II trials. Response rates have ranged from 9% to 17%, suggesting that these particular combinations were not more effective than carboplatin alone. Providing palliation for stage IV NSCLC patients continues to be a major challenge. The low toxicity and modest activity observed with carboplatin suggest that further evaluation of carboplatin is warranted in stage IV NSCLC patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Combined modality therapy for locally advanced non-small cell lung carcinoma.

Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting.

Adult↗
PubMed1990

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy.

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.

Adult↗
PubMed1990

Concurrent chemotherapy and thoracic irradiation in non-small cell lung cancer.

Do results from recently reported phase II trials of combination chemotherapy and concurrent radiation warrant evaluation in a randomized study? Our bias is that only treatment regimens associated with a twofold increase in median survival should be considered for a phase III trial increase in median survival. Therefore, for stage IIIA N2 NSCLC patients median survival should increase from 12 to 24 months, and for stage IIIB patients, it should increase from 9 to 18 months. Although survival results from some combined modality trials are encouraging, thus far no concurrent chemotherapy-radiation regimen appears to have produced the preceding results.

Antineoplastic Agents↗
PubMed1989

A phase II evaluation of cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study.

Cisplatin is one of the most active single agents in advanced squamous cell carcinoma of the cervix and is synergistic with 5-fluorouracil in the laboratory. The Gynecologic Oncology Group has conducted a phase II trial in which cisplatin at 50 mg/ml2 given intravenously on Day 1 was combined with 5-fluorouracil 1000 mg/m2 daily given as a 24-hr infusion on Days 1-5. Treatment was repeated every 21 days. Fifty-five patients were treated with this regimen, resulting in seven complete remissions (12.7%) and five partial remissions (9.1%). The median survival was 6.4 months. Toxic effects of grade 2 or greater were leukopenia in 10 patients (18.2%), thrombocytopenia in 2 patients (3.6%), gastrointestinal effects in 25 patients (45.5%), and renal effects in 1 patient (1.8%). On the basis of these results, the cisplatin and 5-fluorouracil regimen does not appear to have any advantage over cisplatin alone in advanced cervical cancer.

Adult↗
PubMed1988

Elevated creatine phosphokinase MB in a patient with neuroendocrine carcinoma of the colon--evidence for a tumor marker. Report of a case.

Elevated creatine phosphokinase (CPK) MB isoenzyme has become accepted as a highly specific criterion for the diagnosis of myocardial infarction (MI). A patient with metastatic neuroendocrine carcinoma of the colon who had marked and persistent elevation of CPK-MB isoenzyme, in the absence of clinical and cardiographic evidence for MI, is described. The CPK-MB level was 25 percent (normal, less than 3 percent) on admission, 39 percent postoperatively, and 57 percent on discharge. A prompt decline in serum CPK-MB activity (11 percent, less than 3 percent) paralleled chemotherapy-induced tumor regression. Resurgence of the isoenzyme heralded recurrent disease. These findings suggest that CPK-MB may be a valuable adjunct marker in the diagnosis and monitoring of neuroendocrine carcinomas.

Biomarkers, Tumor↗