Biomedical subjects

E T Creagan

Publications and source records attributed to E T Creagan.

At least 55 records · Page 3Linked to original sources

PubMed1989

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↗

PubMed1989

Regional and systemic strategies for metastatic malignant melanoma.

Malignant melanoma is no longer a rare neoplasm. Recreational exposure to sunlight is undoubtedly an etiologic factor. Among all cancers, its rate of increase is exceeded only by that of bronchogenic carcinoma. Before administration of systemic therapy, histologic confirmation of the diagnosis and assessment of both the relative medical fitness of the patient and the available psychosocial support are important. Chemotherapeutic and interferon-alpha regimens may offer transient reprieve in 15 to 20% of patients but yield few long-term survivors. Other biologic response modifiers, such as tumor necrosis factor and interleukin 2, are promising but without established consistent efficacy. Postoperative systemic treatment programs for patients at risk for disseminated disease are of no proven benefit in randomized trials and cannot be endorsed outside of the context of a clinical trial. Radiation therapy may provide useful palliation, especially with a fraction of 400 cGy rather than the more traditional dose of 200 cGy/fraction. Selected patients with metastatic disease may benefit from surgical resection, but residual disease after attempted extirpation is usually associated with prolonged disability.

Antibodies, Monoclonal↗

PubMed1989

A prospective, randomized controlled trial of megestrol acetate among high-risk patients with resected malignant melanoma.

In light of some evidence that hormonal factors may impact on malignant melanoma, we performed a randomized trial of megestrol acetate versus observation among 67 patients with high-risk resected stage I or stage II (nodal) malignant melanoma. Following stratification by relevant prognostic factors, we observed a statistical significance in survival advantage for megestrol acetate that approached 7.6 versus 2.6 years, median survival; two-sided log rank p = 0.06. Disease-free survival was also greater for patients who received this hormonal therapy (3.4 versus 1.1 years, median disease-free survival), but the difference was not statistically significant (two-sided log rank p = 0.20). The most noteworthy side effects were weight gain (median 6-month gain of 8.2 kg) and impotence. Fully recognizing the hazards of limited sample analyses and the need for confirmatory trials, our findings suggest a possible role for megestrol acetate as adjuvant therapy for selected patients with malignant melanoma.

Female↗

PubMed1989

Malignant melanoma: cost and reimbursement issues.

Once malignant melanoma has spread below the epidermis and metastasized, the response rate to conventional therapy is relatively poor. Investigational drug programs currently are exploring a number of promising treatment options, including biologic therapy (alpha interferon and interleukin-2) and immunotherapy. However, the costs of investigational drug therapy are high, and there are signs that the federal government and third-party payers are increasingly reluctant to reimburse patient expenses for participation in clinical drug trials. Unless financial support for investigational therapy is maintained, conventional therapy with low rates of cure will continue to be reimbursed while the use of state-of-the-art research drugs will slow to a halt.

Antineoplastic Agents↗

PubMed1989

Pain relief in terminally ill patients.

A systematic approach to identifying the cause of pain and rational use of drug therapy are keys to providing pain relief to cancer patients. Aspirin, acetaminophen and nonsteroidal anti-inflammatory drugs are effective for mild to moderate pain, and they enhance the effectiveness of weak oral narcotics, such as codeine. For severe pain, morphine is the drug of choice. A variety of adjuvant drugs can be used to enhance the effect of narcotics and to treat specific side effects of the disease or of therapy. For the terminally ill patient, a peaceful death with dignity should always be possible.

Adjuvants, Pharmaceutic↗

PubMed1988

A phase I clinical trial of recombinant human tumor necrosis factor.

We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF-alpha) in 27 patients with advanced solid neoplasms. Therapy consisted of a 30-minute intravenous (IV) infusion on days 1 through 5, every 2 to 3 weeks. Daily doses ranged from 5 micrograms/m2 to 200 micrograms/m2. Dose-limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38 degrees C) were not clearly dose-related between 5 micrograms/m2/d and 150 micrograms/m2/d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3, 1.2 X 10(3)/microliters in two patients) at a dose of 5 micrograms/m2/d and 150 micrograms/m2/d, respectively; and thrombocytopenia (leukocyte count, 73 X 10(3)/microliters) at 10 micrograms/m2/d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/microliters compared with a subsequent median of 462 cells/microliters. We also detected hypertriglyceridemia in all patients. The median baseline increased from 93 mg/dl (range, 56 to 219 mg/dl) to 203 mg/dl (range, 94 to 454 mg/dl). From our experience, a clinically manageable outpatient regimen for Phase II trials consists of rTNF-alpha (150 micrograms/m2) followed by a 1-hour IV infusion of 500 ml of normal saline to abrogate hypotension daily for 5 days every 2 weeks for four cycles, then every 3 weeks thereafter to facilitate recovery from constitutional sequelae.

Adult↗

PubMed1988

A phase I-II trial of the combination of recombinant leukocyte A interferon and recombinant human interferon-gamma in patients with metastatic malignant melanoma.

Twenty patients with advanced malignant melanoma received daily intramuscular recombinant leukocyte A interferon (rIFN-alpha A, Roferon-A, Hoffmann-Laroche, Nutley, NJ) concomitant with recombinant human interferon-gamma (rIFN-gamma Genentech, South San Francisco, CA). During the first week alpha dose was 2 X 10(6) U/m2 and the gamma dose was 0.01 mg/m2 with escalations, if clinically tolerable, during the second week to 5 X 10(6) U/m2 and 0.025 mg/m2, respectively. Twelve patients received the escalated doses; subsequent granulocytopenia and a flu-type illness were severe in four of the 12. We observed one partial response of MRI-documented and biopsy-confirmed osseous metastases for 7+ months. For all study participants, the median time to progression was 1 month with a median survival of 6 months. From the dose and schedule which we utilized, concurrent rIFN-alpha A and rIFN-gamma provided little impact on advanced malignant melanoma.

Adult↗

PubMed1988

Cisplatin-based chemotherapy for neoplasms arising from salivary glands and contiguous structures in the head and neck.

We observed a 38% response rate from platinum-based chemotherapy among 34 patients with locally recurrent or disseminated neoplasms from salivary glands or contiguous structures. Adenocarcinoma was the predominant histology. Eleven patients manifested partial response or regression, and two had complete regressions of soft tissue disease. The most durable visceral responses were partial regressions (lung, 11 months; and central nervous system, 34 months). Eleven of the 13 responders showed tumor regression within 3 months of commencing therapy, and the median response duration was 7 months (range 2-34 months). The median survival among all 34 patients was 15 months, and was 18 months among the 13 responders. Hence, a response to treatment did not necessarily confer any long-term survival advantage. Although gastrointestinal toxicities were troublesome with the earlier regimens, contemporary antiemetics (dexamethasone, metoclopramide) have substantially modified these sequelae. Platinum programs may provide useful palliation for selected patients with these neoplasms, but the impact on survival is negligible.

Adult↗

PubMed1988

An evaluation of recombinant leukocyte A interferon with aspirin in patients with metastatic renal cell cancer.

The authors designed a clinical trial to assess the impact of aspirin (ASA) (600 mg four times daily) on the constitutional sequelae of recombinant leukocyte A interferon (IFN-alpha 2A), 20 X 10(6) U/m2 thrice weekly, in 29 patients with advanced renal cell cancer (RCC). Aspirin provided no meaningful amelioration of side effects compared to our prior experience of IFN-alpha 2A alone. Interestingly, the objective response rate of 34% (10/29) was considerably higher than the 15% recently reported from an aggregate of 344 patients participating in 14 prospective clinical trials. In light of small numbers, subtle selection biases, and the well-recognized hazards of retrospective analyses, currently it is unclear if the apparent therapeutic advantage from ASA plus IFN-alpha 2A reflects chance occurrence or therapeutic potentiation from ASA. A randomized trial is planned to determine if ASA may have enhanced the efficacy of IFN-alpha 2A in patients with advanced RCC.

Anorexia↗

PubMed1988

Recombinant leukocyte A interferon with doxorubicin. A phase I study in advanced solid neoplasms and implications for hepatocellular carcinoma.

A pilot study was performed on seven patients with advanced solid neoplasms. They received recombinant leukocyte interferon A (rIFN-alpha A) 12 X 10(6) U/m2 intramuscularly daily for 5 days plus doxorubicin, 25 mg/m2 IV on day 3 of each monthly cycle (Roferon-A, Hoffman-LaRoche, Nutley, NJ). Because of side effects, the dose was not increased above the initial level. There was a striking partial response of biopsy-confirmed hepatocellular carcinoma for 6+ months along with a decrease in alpha-fetoprotein from 39,000 to 202 ng/mL. The doxorubicin dose is approximately 33% to 42% of the typical single-agent dose, thus suggesting that the clinical toxicity from these two agents is additive.

Adult↗

PubMed1988

Recombinant interferons in the management of advanced malignant melanoma. Updated review of five prospective clinical trials and long-term responders.

One hundred forty-five patients with disseminated malignant melanoma have participated in five Phase II clinical trials utilizing leukocyte A recombinant interferon (IFN-alpha 2A) (96 patients), recombinant interferon gamma (rIFN-gamma) (29), or IFN-alpha 2A concomitant with rIFN-gamma (20 patients). The overall response rate was 17%, with most regressions occurring with the IFN-alpha 2A regimens. The median times to progression (1 month) and survival (6 months) were generally similar to those from chemotherapeutic agents. However, a limited cohort of patients had complete regressions or durable partial responses even after treatment was discontinued or maintained at less than or equal to 25% of the starting dosage. Most objective regressions were partial, occurred in nonvisceral sites, and were detected within 2 months of the beginning of therapy. The most noteworthy sequelae from these regimens were predominantly constitutional, but without any obvious long-term complications. These interferon programs can be conveniently self-administered on an outpatient basis. Although single-agent interferon regimens for advanced malignant melanoma will probably not offer a substantive therapeutic advance, combinations of these molecules with other biological agents (tumor necrosis factor), biochemical modulators (difluoromethylornithine), and cytotoxic agents (bischloroethylnitrosourea, BCNU) offer innovative therapeutic dimensions in the design of future clinical investigations.

Adult↗

PubMed1988

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↗

PubMed1988

Pilot study of a continuous five-day intravenous infusion of etoposide concomitant with cisplatin in selected patients with advanced cancer.

In view of experimental and clinical data suggesting enhanced antiproliferative efficacy from a continuous infusion of etoposide (VP-16) concomitant with cisplatin (CDDP), we performed a dose-seeking study of a five-day infusion of VP-16, 30 mg/m2/24 h and CDDP, 18.5 to 25 mg/m2/24 h. Among eight patients with advanced solid tumors, dose-limiting toxicities were leukopenia and thrombocytopenia. There were no clinically significant renal, neurologic, or otologic sequelae. Nausea and vomiting were mild and transient. Although the trial was not designed as a phase II assessment, we observed three objective regressions among three patients with advanced gastric adenocarcinoma who had failed prior chemotherapy. The total CDDP dose is similar to five-day single agent studies, yet the total VP-16 dose is approximately 24% to 50% less than a five-day single agent VP-16 dose. The recommended regimen for continuous 120-hour infusion is VP-16, 30 mg/m2/24 h and CDDP, 20 mg/m2/24 h, repeated at monthly intervals.

Adenocarcinoma↗

PubMed1988

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↗

PubMed1987

Three consecutive phase II studies of recombinant interferon alfa-2a in advanced malignant melanoma. Updated analyses.

In three consecutive Phase II trials of recombinant interferon alfa-2a (rIFN alfa-2a; Roferon-A Hoffmann-La Roche, Nutley, NJ) involving 96 patients with advanced malignant melanoma, an overall response rate of 22% was observed. For all study participants, the median time to disease progression was 1.7 months, and the median survival was six months. Most regressions occurred within one month of commencing therapy, were usually limited to soft tissue metastases, and were transient. However, responses in three patients were long term, lasting 32+, 36+, and 41+ months. A thrice weekly intramuscular dose of 50 x 10(6) U/m2 produced an intolerable flulike illness concomitant with a median weight loss of 5.6 kg. The addition of cimetidine to the same dose in 35 patients was of no therapeutic value. A dose of 12 x 10(6) U/m2 produced clinically acceptable toxicities, and a median weight loss of 2.1 kg. There was no apparent dose response relationship, nor were there any obvious sequelae from antibody formation to interferon alfa-2a. As single agent therapy in malignant melanoma, interferon alfa-2a was only marginally useful in most patients. Nevertheless, combination regimens of this agent with cytotoxic agents, alternative molecular species of interferon, and lymphokines, notably tumor necrosis factor, offer a conceptually intriguing dimension in the design of future clinical trials.

Adjuvants, Immunologic↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma.

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.

Alanine↗