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Biomedical subjects

P J Loehrer

Publications and source records attributed to P J Loehrer.

At least 19 recordsLinked to original sources
PubMed2002

Epidermal growth factor receptor expression in invasive thymoma.

PURPOSE: Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity. Activation results in a variety of cellular responses including cell proliferation and differentiation. In clinical trials, anti-EGFR is showing promise in the treatment of solid tumors expressing EGFR. Thus, we assessed EGFR expression in a series of thymic epithelial tumors. METHODS: Tumors from 37 patients seen at Indiana University School of Medicine (IUMC) for treatment of thymoma (31 patients) or thymic carcinoma (six patients) were assessed for EGFR expression. Five-micron sections of formalin-fixed, paraffin-embedded tumor (28 invasive and/or metastatic thymomas, six thymic carcinomas, and three non-invasive thymomas) were stained with anti-EGFR. Any degree of cytoplasmic membrane staining of tumor cells was considered positive; furthermore, staining was scored 0 to 3+ using criteria as standardized for HER-2/neu assessment of breast carcinoma. Appropriate controls were performed. RESULTS: Positive staining of tumor was observed in 28 tumors (23 invasive and/or metastatic thymomas, two thymic carcinomas, and three non-invasive thymomas). CONCLUSIONS: EGFR is expressed in a high percentage of thymic epithelial tumors. EGFR is often strongly expressed and is a potential therapeutic target in patients with malignant thymic tumors. We are pursuing additional studies to assess anti-EGRF in the treatment of patients with advanced thymoma.

Adult↗
PubMed2002

Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer: a Hoosier Oncology Group randomized study.

BACKGROUND: We performed this phase III study to determine whether the addition of 3 months of oral etoposide in non-progressing patients with extensive small-cell lung cancer (SCLC) treated with four cycles of etoposide plus ifosfamide plus cisplatin (VIP) improves progression-free survival (PFS) or overall survival. PATIENTS AND METHODS: Patients with extensive SCLC with a Karnofsky performance score (KPS) > or =50, adequate renal function and bone marrow reserve were eligible. Patients with CNS metastasis were eligible and received concurrent whole-brain radiotherapy. All patients received etoposide 75 mg/m2, ifosfamide 1.2 g/m2 and cisplatin 20 mg/m2 intravenously on days 1-4 every 3 weeks for four cycles. Non-progressing patients were randomized to oral etoposide 50 mg/m2 for 21 consecutive days every 4 weeks for three courses versus no further therapy until progression. RESULTS: From September 1993 to June 1998, 233 patients were entered and treated with VIP with 144 non-progressing patients subsequently randomized to oral etoposide (n = 72) or observation (n = 72). Minimum follow up for all patients is 2 years. Toxicity with oral etoposide was mild. There was an improvement in median PFS favoring the maintenance arm of 8.23 versus 6.5 months (P = 0.0018). There was a trend towards an improvement in median (12.2 versus 11.2 months), 1-year (51.4% versus 40.3%), 2-year (16.7% versus 6.9%) and 3-year (9.1% versus 1.9%) survival (P = 0.0704) favoring the maintenance arm. CONCLUSIONS: Three months of oral etoposide in non-progressing patients with extensive SCLC was associated with a significant improvement in PFS and a trend towards improved overall survival.

Administration, Oral↗
PubMed2001

Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial.

BACKGROUND: Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced thymoma and thymic carcinoma. METHODS: From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m2 on Days 1-4) ifosfamide (1.2 g/m2 on Days 1-4), and cisplatin (20 mg/m2 on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. RESULTS: Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. CONCLUSIONS: The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease.

Adult↗
PubMed2001

Thymic malignancies.

Thymomas and thymic carcinomas are unique tumors of the anterior mediastinum. The association of a variety of different paraneoplastic syndromes with such lesions has fascinated physicians and researchers for years. Most recently, it has been demonstrated by numerous authors that thymomas are chemosensitive tumors. Their indolent nature and relative rarity have made evaluation through prospective randomized clinical trials extremely difficult. Further information regarding the molecular nature of these neoplasms and immunologic aspects is needed in future investigation.

Adrenal Cortex Hormones↗
PubMed2001

Altretamine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group trial.

Thirty patients with advanced renal cell carcinoma were treated on a phase 11 trial with altretamine. Altretamine was administered orally at a dosage of 260 mg/m2 days 1 through 14 with cycles repeated every 28 days. Nausea and vomiting were the most common toxicities. Ten percent (3 of 30) experienced Grade 3 gait abnormalities. None of the thirty evaluable patients achieved a complete or partial response. In summary, altretamine did not show antitumor activity in the treatment of advanced renal cell carcinoma.

Adult↗
PubMed2001

High-dose carboplatin with etoposide in patients with recurrent thymoma: the Indiana University experience.

Thymoma is a chemotherapy-sensitive tumor with a 30-50% 5-year survival in previously untreated patients. Unfortunately, durable CRs with salvage chemotherapy are rarely observed. We initiated a phase II trial of high-dose carboplatin and etoposide in patients with relapsed thymoma or thymic carcinoma. All patients had progressive disease (PD) after initial or salvage chemotherapy, but were not cisplatin-refractory. PBSCs were mobilized using 10 microg/kg/day G-CSF. Patients received carboplatin 700 mg/m(2) and etoposide 750 mg/m(2) i.v. on days -5, -4, -3. Five patients were enrolled and evaluated after tandem transplants 4 weeks apart. All patients had pleural-based and lung parenchymal metastasis, one or two prior surgeries and two or more courses of prior cisplatin-based chemotherapy regimens. Chemotherapy was well tolerated, although grade IV hematological toxicity occurred in all patients. Progression-free survival following HDC ranged from 3.5 to 16.5 months. One patient maintained a CR for 12.8 months, then died from an unrelated cause. With a minimum of 2 years follow-up for all patients, three of five patients remain alive at 26+, 36+, and 49+ months. High-dose carboplatin and etoposide in relapsed thymoma is feasible with acceptable toxicity; however, these limited data do not appear superior to standard-dose salvage therapy.

Adult↗
PubMed2000

Activity of multitargeted antifolate (pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma: results from a phase II study.

BACKGROUND: The aim of this study was to confirm the activity and assess the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS: Forty-six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m(2) as a 10-minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS: Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 15.4% (95% confidence interval [CI], 4.1-26. 7%) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95% CI, 10.5-17.0%); 65% of patients were alive at 1 year, and the median time to progression was 4.4 months (range, 3.2-5.7 months). The main toxicities were hematologic, with common toxicity criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropenia (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminases (23%). Dose omissions were not required and 21% of doses were reduced. CONCLUSIONS: MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency.

Adult↗
PubMed2000

Phase II study of the multitargeted antifolate LY231514 (ALIMTA, MTA, pemetrexed disodium) in patients with advanced pancreatic cancer.

PURPOSE: To determine the safety and activity of LY231514 (ALIMTA, MTA, pemetrexed disodium, Eli Lilly and Co., Indianapolis, IN) in chemotherapy-naïve patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with unresectable or metastatic pancreatic cancer received LY231514 600 mg/m2 as a 10-minute infusion every three weeks. RESULTS: Forty-two patients were enrolled in this phase II trial. The median age was 60.3 (range 37-77) years; 79% had metastatic disease. Neutropenia was common (40% of patients > or = grade 3) but infectious complications were rare. Significant anemia or thrombocytopenia occurred in < 20% of patients. Non-hematologic toxicities included grade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevations of bilirubin or transaminases were infrequent (< 25% of patients) and did not require dose reductions or treatment delays. Thirty-five patients received two cycles of therapy and were evaluable for response. One complete (duration 16.2 months) and one partial (duration 6.9 months) were observed resulting in an objective response rate of 5.7% for evaluable patients. In addition, 17 patients (40%) had stable disease that lasted > or = 6 months in 5 patients. The median survival was 6.5 months, with 28% of patients alive at one year. CONCLUSIONS: LY231514 is a well-tolerated agent with minimal objective antitumor activity in pancreatic cancer. The median and one year survival times, which may be important indicators in phase II trials of new agents, are of interest. Combination trials of LY231514 in pancreatic cancer are planned.

Adenocarcinoma↗
PubMed1999

Sacrococcygeal teratoma in adults: case reports and a review of the literature.

BACKGROUND: The sacrococcygeal area is the most frequent site of teratoma in infants, but it is a rare location for teratoma in adults. METHODS: The authors report two patients in their sixth decade of life with the pathologic diagnosis of sacrococcygeal teratoma. The clinical presentations, the histologic findings, and the patients' clinical outcomes are described. A review of the literature on sacrococcygeal teratoma in adults is also presented. RESULTS: In the first patient, who had no evidence of recurrence after adequate resection, examination of the specimens showed mature teratoma. The second patient had mature teratoma with adenocarcinomatous component and possible leptomeningeal involvement. She died 2 months after the operation. CONCLUSIONS: Although rare in adults, sacrococcygeal teratoma should be considered in the differential diagnosis of patients with a pelvic mass presenting with obstructive symptoms. These two cases suggest that sacrococcygeal mature teratoma is surgically curable if teratoma is completely resected. The presence of leptomeningeal involvement and malignant transformation are associated with a less favorable outcome.

Adenocarcinoma↗
PubMed1999

Thymoma: state of the art.

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localized tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma.

Antineoplastic Agents↗
PubMed1999

Current approaches to the treatment of thymoma.

Thymoma is an unusual tumour, but it is the most common malignancy in the anterior mediastinum. This tumour is unique in its frequent association with paraneoplastic syndrome and its potential for indolent growth. The distinction between thymomas and other tumours which arise in the anterior or superior mediastinum is important, and the optimal therapy for these malignancies is quite different. Indeed, even in advanced disease, systemic therapy may not only prolong the disease-free survival, but may also be curative in various malignancies. The therapy for patients with thymoma has been evolving over the past few years.

Combined Modality Therapy↗
PubMed1998

Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.

BACKGROUND: Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy. METHODS: We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status. RESULTS: Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall, the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease. CONCLUSIONS: The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.

Adenocarcinoma↗
PubMed1998

Topotecan in previously treated advanced urothelial carcinoma: an ECOG phase II trial.

BACKGROUND: [corrected] Chemotherapeutic agents are playing an increasing role in the management of urothelial carcinoma. Despite recent advances in the treatment of this disease there continues to be a need to identify new active agents and their toxicity spectra. Topotecan is an agent as yet unstudied in bladder cancer. METHODS: Ambulatory patients with progressive advanced urothelial carcinoma following prior systemic chemotherapy were treated with topotecan 1.5 mg/m2 intravenously (i.v.) daily for 5 days every three weeks for 6 cycles. Doses were modified for leukopenic fever, thrombocytopenic bleeding, and any grade 3 or 4 (NCI common toxicity criteria) toxicity. RESULTS: Forty-four eligible patients entered the trial. There were 4 partial responses for an overall response rate of 9.1% (exact 95% two-stage binomial CI, 2.9% to 25.5%). Major identified toxicities were gastrointestinal and myelosuppression. There were no treatment-related deaths. CONCLUSIONS: Topotecan at this dose and schedule has minimal activity in previously treated patients with advanced urothelial carcinoma. Toxicities can be severe but are manageable.

Adult↗
PubMed1998

Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours, with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.

Adult↗
PubMed1998

Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study.

PURPOSE: To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors. PATIENTS AND METHODS: A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed. RESULTS: Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP. CONCLUSION: BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.

Adult↗
PubMed1998

Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor.

PURPOSE: This study was designed to assess the effectiveness of vinblastine, ifosfamide, and cisplatin (VeIP) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide, usually in combination with bleomycin. PATIENTS AND METHODS: From July 1984 through December 1989, 135 patients with progressive, disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP. Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible. Progression was documented by biopsy or increasing serum markers. No exclusion was made on the basis of metastatic site or performance status. The dosages were vinblastine 0.11 mg/kg/d (days 1 and 2), ifosfamide 1.2 gm/m2/d (days 1 through 5), and cisplatin 20 mg/m2/d (days 1 through 5), with courses repeated every 21 days for four cycles. RESULTS: Sixty-seven (49.6%) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma. Overall, 42 (32%) patients are alive and 32 (23.7%) are continuously free of disease. None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries. Two of three extragonadal seminomas are continuously disease-free. CONCLUSION: VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy. Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗