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Biomedical subjects

R T Eagan

Publications and source records attributed to R T Eagan.

At least 19 recordsLinked to original sources

Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognosis.

Between 1975 and 1985, 25 patients with metastatic bronchioloalveolar carcinoma and 223 patients with metastatic adenocarcinoma of the lung received experimental cisplatin-based chemotherapy at the Mayo Clinic. The chemotherapeutic response rates were 32% and 33%, respectively. The median times to progression of disease were identical (3 months in both groups). The median survival times were 4 months and 6 months, respectively. Metastatic bronchioloalveolar carcinoma is an aggressive disease that is associated with a poor prognosis, similar to metastatic adenocarcinoma of the lung.

Adenocarcinoma

Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung.

From October 1979 to December 1982, 126 patients with locally advanced unresectable or inoperable Stage II (7 patients), Stage IIIA (81 patients), and Stage IIIB (38 patients) non-small cell carcinoma of the lung were treated in a prospective randomized trial using five cycles of CAP (Cytoxan, Adriamycin, and cisplatin), T-CAP (triazinate plus CAP), or V-CAP (VP-16 plus CAP) chemotherapy with thoracic radiation therapy (TRT). TRT consisted of 40 Gy in 10 fractions (split-course) with cycles 3 and 4 of chemotherapy. The treatment field included the primary tumor, ipsilateral hilum, mediastinum, and ipsilateral supraclavicular fossa. All patients were followed until death or for a minimum of 5 years for survivors. The evaluable subgroup consisted of 102 patients who completed TRT. Median and 5-year survivals for the entire group were 14.0 months and 10%, respectively; for the evaluable subgroup, they were 14.8 months and 12%, respectively. There was a trend toward better survival with V-CAP plus TRT than with CAP plus TRT (p = 0.08). Median and 5-year survivals were 16.2 months and 18%, respectively, with V-CAP plus TRT. Of eight prognostic variables analyzed for their association with survival, only Eastern Cooperative Oncology Group performance status (0,1 versus 2) (p = 0.02) and weight loss (less than or equal to 10% versus greater than 10%) (p = 0.05) were significant. Sex, age, T stage, N stage, overall stage, and histologic type were not significantly associated with survival. Failure analysis revealed 83 patients (81%) with identifiable first failures. The median time to first failure was 9.8 months, and the median survival after first failure was 4.7 months. Failure patterns included local failure alone (19%), local and distant (20%), and distant alone (43%). Nineteen percent of patients had no documented progression. Total failure patterns were local in 39% and distant in 63%. Twenty-three patients (23%) had failure in the brain; they accounted for 31% of all distant failures. In 20 of these patients (20% of all patients), this was the only site of failure. There were eight (8%) initial nodal failures in 96 untreated contralateral supraclavicular fossae. No initial failures were seen in any of 101 untreated contralateral hila. The data suggest the following: (a) Combined treatment with V-CAP and TRT yielded excellent results (median survival, 16.2 months; 5-year survival, 18%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation.

The cases of 283 small cell lung cancer patients who received treatment with combination chemotherapy with or without prophylactic cranial irradiation (PCI) were reviewed to determine the incidence of leukoencephalopathy. The overall incidence was 10%. Of all patients receiving PCI, 17% developed neurotoxicity, and of those receiving PCI and surviving greater than or equal to 1.5 years, 37% suffered neurologic sequelae. In those receiving PCI but surviving less than 1.5 years, the incidence of neurotoxicity was 4%. The mean time interval between the end of PCI and the onset of neurotoxicity was 17 months (range 2-63 months). The PCI dose ranged from 2600-3600 cGy. None of the patients not receiving PCI developed neurotoxicity. The incidence of neurotoxicity in long-term survivors (greater than or equal to 1.5 years) with respect to PCI dose was less than or equal to 3000 cGy (25%), 3200 cGy (56%), 3600 cGy (36%). Almost all of the patients getting PCI also received lomustine, an agent associated with DNA repair inhibition and synergism with DNA damaging agents such as ionizing radiation or alkylating agents. Under the conditions of our study, PCI was associated with an unacceptable risk of neurotoxicity. Until further information is forthcoming, one should proceed with caution when using PCI in conjunction with lomustine.

Antineoplastic Combined Chemotherapy Protocols

A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer.

One hundred eight eligible patients with advanced, metastatic non-small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, and cisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non-cross resistance.

Aged

Treatment toxicities in long-term survivors of limited small cell lung cancer.

A total of 211 patients with limited small cell lung cancer were assessed retrospectively for long-term toxicities, treatment-related deaths, and second primaries. All had received treatment with various combinations of doxorubicin, vincristine, cisplatin, lomustine, cyclophosphamide, and etoposide with or without split-course thoracic radiotherapy (4,000 cGy/10 fractions) and/or split-course prophylactic cranial irradiation (3,600 cGy/10 fractions). Sixty-eight (32%) of the patients survived longer than 1.5 years and formed the basis of this study. Debilitating pulmonary, cardiac, and neurologic toxicity was noted in 12%, 14%, and 15%, respectively, of long-term survivors. These complications were the result of aggressive combined modality therapy. Certain drugs appeared to cause additive toxicity when combined with radiation. Three patients developed new primary tumors of squamous cell origin. Attention must be directed to defining the safest way to employ aggressive combined modality treatment for these patients.

Antineoplastic Combined Chemotherapy Protocols

Comprehensive phase II evaluation of aziridinylbenzoquinone (AZQ, diaziquone) in recurrent human primary brain tumors.

Ninety-three patients with primary intracranial brain tumors recurrent after cerebral irradiation were treated with aziridinylbenzoquinone (AZQ; Diaziquone). Twenty-four (26%) had tumor regression lasting a median of 9.2 months. Prior chemotherapy was not significantly associated with tumor regression but was associated with survival (median 7.3 months no prior chemotherapy versus 4.7 months with prior chemotherapy; logrank p = 0.03). AZQ demonstrated anti-tumor activity in a wide variety of primary intracranial neoplasms recurrent after radiation therapy and deserves study in patients at the time of diagnosis. We believe alternating or combining AZQ and BCNU should be rewarding. The principal toxicity of AZQ is myelosuppression.

Adolescent

Cyclophosphamide, etoposide, and infusion cisplatin in refractory small cell lung cancer. A preliminary report.

Twelve patients (three with limited and nine with extensive disease) with small cell carcinoma of the lung who had plateaued or progressed on their chemotherapeutic regimens were switched to a program of combination chemotherapy consisting of cyclophosphamide, etoposide, and a 5-day continuous infusion of cisplatin. Nine of the 12 patients (75%) showed further tumor reduction, including four patients who achieved a clinical complete response. Also noted was a patient who previously failed on a regimen of short infusion cisplatin who responded to the continuous infusion platinum regimen. Toxicity was quite acceptable, considering the amount of prior treatment given these patients. Further studies seem warranted to confirm these encouraging preliminary results.

Antineoplastic Combined Chemotherapy Protocols

Lack of value for cisplatin added to mitomycin-doxorubicin combination chemotherapy for carcinoma of unknown primary site. A randomized trial.

Fifty-five patients with metastatic carcinomas of unknown primary site (50 adenocarcinomas) were randomized, after stratification, to treatment with either mitomycin and doxorubicin (MA) or mitomycin, doxorubicin, and cisplatin (MAP). There was a moderate but nonsignificant improvement in regression frequency (14 vs. 27%) and a slight but also nonsignificant worsening of survival (median 5.5 months vs. median 4.6 months) by the addition of cisplatin at 60 mg/m2 to the MA regimen.

Adult

No routine role for vincristine, adriamycin, and cyclophosphamide (VAC) or thoracic radiation therapy in extensive stage small cell lung cancer.

A randomized trial of extensive small cell lung cancer (SMCLC) without CNS metastases comparing combination chemotherapy with the three-drug combination of vincristine, doxorubicin, and cyclophosphamide (VAC) versus a program using six drugs and starting with VAC plus Lomustine (CCNU) and etoposide (VAC-LE) was begun. After three cycles, patients without progression of disease were bronchoscoped and then randomized to the original chemotherapy program and prophylactic cranial irradiation (PCI) with or without thoracic radiation therapy (TRT). Patients with CNS metastases at diagnosis were treated with the VAC-LE program. At initial evaluation of 17 patients on VAC, and 18 without CNS metastases, and 10 with CNS metastases on VAC-LE, a statistical superiority for the VAC-LE over VAC was noted. Patients on VAC-LE (in CNS negative patients) had a higher regression rate (89 vs. 82%, 7 CR vs. 0%); a higher negative second bronchoscopy rate (69 vs. 50%); and better median (12.3 vs. 6.8 months), 2-year (14 vs. 0%), and overall survival rates (p = 0.005) than did patients on VAC. Even the VAC-LE, CNS positive patients had higher CR (20 vs. 0%), median (8.6 vs. 6.8 months), and 2-year survival rates (10 vs. 0%) than did VAC patients without CNS metastases.

Antineoplastic Combined Chemotherapy Protocols

Delayed leukoencephalopathy in survivors with small cell lung cancer.

Six patients with small cell lung cancer developed a slowly progressive neurologic syndrome characterized by apathy, abulia, memory loss, gait ataxia, and corticospinal tract signs 26 to 50 months (mean, 35.2 months) after prophylactic cranial irradiation and systemic chemotherapy. In each case this was accompanied by CT and/or MRI evidence of changes in the periventricular white matter. These patients are long-term survivors (41 to 69 months) and do not have CNS metastases.

Adult

Pilot study of induction therapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) and chest irradiation prior to thoracotomy in initially inoperable stage III M0 non-small cell lung cancer.

In an attempt to increase the resection rate of patients with non-small cell lung cancer, two cycles of cyclophosphamide, doxorubicin, and cisplatin chemotherapy and chest irradiation (3000 cGy in 10 fractions, split course) were administered to 42 initially inoperable (T3 or N2M0) patients. Three patients were subsequently determined to be ineligible, two because of small cell histology and one because of M1 disease. Among the 39 eligible patients, 20 (51%) had a regression following the combined-modality therapy. Seventeen of these patients plus two with stable disease had thoracotomy. Complete surgical resection was accomplished in 13 patients (33% of all eligible 39 patients; 68% of all 19 patients who had thoracotomy). There were no statistically significant survival differences between patients not having thoracotomy and those who had thoracotomy (or even those with complete tumor excision). The patients with chemotherapy, chest irradiation, and surgical resection had a low incidence of local in-chest failure (5%), but distant failure was still a major problem.

Aged

Phase II study of the three-drug combination of mitomycin C, CCNU, and methotrexate (MCM) in advanced non-small cell lung cancer.

Ninety-two patients with advanced non-small cell lung cancer, 51 without prior chemotherapy exposure, were treated with the combination of mitomycin C, lomustine (CCNU), and methotrexate (MCM). Overall, the regression rate was 33%, the median regression duration 4.9 months, and the median survival 4.9 months. Patients with ECOG performance scores (PSs) of 0-1 had a statistically significant higher regression rate than did patients with ECOG PSs of 2-3 (43% versus 15%; p = 0.005) as did patients without prior chemotherapy (41% versus 22%; p = 0.05). Cell type and prior chemotherapy exposure did not affect regression duration, time to progression, nor survival. Subjective toxicity was quite acceptable. Cumulative myelosuppression was the most significant objective toxicity. MCM is a relatively effective combination chemotherapy regimen, even in patients with prior chemotherapy exposure (predominantly doxorubicin and cisplatin-based chemotherapy).

Adult

Differing response rates and survival between squamous and non-squamous non-small cell lung cancer. Comparison of CAP versus MAP.

One hundred and thirty patients with advanced non-small cell lung cancer were treated in a randomized study with either CAP (cyclophosphamide, doxorubicin, and cisplatin) or MAP (mitomycin C, doxorubicin, and cisplatin). Among all patients, regardless of cell type, the regression rate was slightly higher for MAP (46%) than CAP (34%) but no differences were detected in time to progression and overall survival. However, differences were apparent by treatment when patients were divided into two groups: squamous cell (SQC) and non-squamous cell (non-SQC). MAP, compared to CAP, was associated with a significantly superior regression rate (60% vs. 33%), time to progression, and overall survival in SQC. On the other hand, CAP, compared to MAP, was associated with a significantly longer overall survival in non-SQC. This apparent difference among subtypes of non-small cell lung cancer in response to chemotherapy regimens differing only in one drug, if confirmed, will need to be kept in mind in designing future studies.

Adult

Continuous five-drug versus alternating three-drug and two-drug chemotherapy after five-drug or three-drug induction in extensive small cell lung cancer.

Fifty-six patients with extensive small cell lung cancer were treated with vincristine, doxorubicin, cisplatin, etoposide, and cyclophosphamide in a prospective randomized trial using all five drugs together or as three-drug (cisplatin, etoposide, cyclophosphamide) and two-drug (doxorubicin, vincristine) combinations given sequentially, then alternatively. The five-drug combination was associated with a higher overall regression rate (p = 0.03), higher complete regression rate (p = 0.09), prolonged time to first progression (p = 0.03), more nervous system initial failures (p = 0.07), more anemia requiring transfusion (p = 0.04), but no prolongation of overall survival (median 332 days for five-drug, median 303 days for three-drug and two-drug). Until more and better chemotherapeutic agents become available, little or no advantage is likely to be gained for patients with small cell lung cancer given sequential, or alternating chemotherapy.

Adult

Dianhydrogalactitol and radiation therapy. Treatment of supratentorial glioma.

Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma.

Adult

VP-16, cyclophosphamide, adriamycin and cis-platinum (V:CAP-I) in patients with metastatic adenocarcinoma of the lung.

In an attempt to improve upon the 42% regression rate of the CAP-I regimen in patients with advanced adenocarcinoma of the lung, VP-16 was added to that regimen. VP-16, as a single agent, had a response rate of 12.5% (3/24) In a similar group of patients. The new regimen, V:CAP-I, had a tumor regression rate of 35% (7/20) and an estimated median survival of 171 days. Hence, we were unable to conclude that the addition of VP-16 to the CAP-I regimen statistically improved the regression rate of the CAP-I regimen.

Adenocarcinoma