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Biomedical subjects

R B Livingston

Publications and source records attributed to R B Livingston.

At least 19 recordsLinked to original sources
PubMed1992

Phase II evaluation of high-dose intravenous cisplatin for treatment of adult malignant gliomas recurrent after chloroethylnitrosourea failure.

Twenty-one patients with recurrent malignant glioma who had failed prior chemotherapy with nitrosoureas were treated with high-dose intravenous cisplatin on days 1 and 8 of successive 4 week cycles. Fourteen patients were evaluable for response. Four patients showed partial responses; mean time to tumor progression (MTP) was 8 weeks. Six patients stabilized; MTP was 11 weeks. Four patients showed no response. There were no infectious or hemorrhagic complications, but partial hearing loss occurred in 7 patients and severe vomiting in 8 patients. High-dose intravenous cisplatin demonstrates substantial activity against malignant gliomas recurrent after chloroethylnitrosourea (CENU) failure.

Adult↗
PubMed1991

Alternating weekly doxorubicin and 5-fluorouracil/leucovorin followed by weekly doxorubicin and daily cyclophosphamide in stage IV breast cancer. A Southwest Oncology Group study.

Twenty-seven women with metastatic breast cancer were treated with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) every other week, alternating with 5-fluorouracil (5FU) and high-dose calcium leucovorin, for a 12-week induction regimen, followed by weekly doxorubicin and oral daily cyclophosphamide. Twenty-five women were eligible and evaluable. Of these, complete response occurred in two patients (8%) and partial response in six patients (24%), for a total response rate of 32%. Toxicity was similar to that seen in previous Southwest Oncology Group (SWOG) trials in this patient population. Response rates in this study were inferior, with comparable median survivals to those of previous SWOG studies that are reviewed. Additional, more dose-intensive approaches incorporating newer approaches to the administration of cancer chemotherapeutic agents are planned.

Adenocarcinoma↗
PubMed1991

Cisplatin and novobiocin in the treatment of non-small cell lung cancer. A Southwest Oncology Group study.

Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin. Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four cycles) after steady-state dosing with novobiocin (1000 mg or four 250-mg capsules every 12 hours for six doses, four of which were administered before each dose of cisplatin). One patient remains on study and cannot be evaluated for response. No complete responses were seen. Three patients (8%) had partial responses and an additional patient had an unconfirmed partial response. The median survival time of all patients was just less than 7 months. These results are comparable with those of other concurrent Southwest Oncology Group (SWOG) Phase II and III trials of high-dose cisplatin in non-small cell lung cancer (NSCLC). Novobiocin plasma levels were obtained for three patients and were approximately 50% of the optimal concentration as reported in cell culture for potentiation of cytotoxicity. It was concluded that an optimum test of novobiocin as a modulator of cytotoxicity may require the availability of an intravenous preparation.

Administration, Oral↗
PubMed1991

A weekly cisplatin-based induction regimen for extensive non-small cell lung cancer. A Southwest Oncology Group study.

The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach.

Adult↗
PubMed1991

Pneumocystis carinii pneumonia associated with profound lymphopenia and abnormal T-lymphocyte subset ratios during treatment for early-stage breast carcinoma.

Two women with Stage II breast carcinoma treated with lumpectomy followed by breast irradiation and adjuvant chemotherapy developed Pneumocystis carinii pneumonia while receiving cytotoxic chemotherapy. Neither woman had evidence of immunosuppression before therapy. They both had profound lymphopenia, reversed CD4/CD8 ratios, and normal peripheral blood total leukocyte counts at the time of their infections. Both women were seronegative for human immunodeficiency virus type 1 and had no risk factors for such an infection. The patients' CD4 lymphocyte counts increased after chemotherapy for breast carcinoma was discontinued. Thus, it appears that the therapy they received may have caused severe T-lymphocyte mediated immunosuppression.

Adult↗
PubMed1991

Treatment of non-small-cell lung cancer with vinblastine and very high-dose cisplatin. A Southwest Oncology Group study.

Suggestions of a dose-response effect for cisplatin in non-small-cell lung cancer have contributed to the development of very high-dose cisplatin regimens (200 mg/m2 per cycle). We treated 53 eligible patients with metastatic or recurrent non-small-cell lung cancer with a combination of 100 mg/m2 cisplatin and 4 mg/m2 vinblastine, each given on days 1 and 8 of a 28-day cycle. We observed no complete response and 4 partial responses (8%). Median survival was 6 months. Toxicities of grade III or greater included leukopenia (11 cases), nausea/vomiting (6 cases), thrombocytopenia (2 cases), anemia (2 cases), and elevation of transaminase (1 case). Neurotoxicity has been reported to be a major problem in several other very high-dose cisplatin regimens. The low level of neurotoxicity observed in this study may be attributable to the median cumulative cisplatin dose of less than 600 mg/m2. This vinblastine/very high-dose cisplatin regimen showed minor activity against non-small-cell lung cancer. The level of activity did not surpass that of standard-dose (100 mg/m2 per cycle) cisplatin-containing regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Treatment of limited small-cell lung cancer with concurrent etoposide/cisplatin and radiotherapy followed by intensification with high-dose cyclophosphamide: a Southwest Oncology Group study.

Between March 1986 and May 1988, the Southwest Oncology Group enrolled 58 previously untreated patients with limited small-cell lung cancer on a treatment program that administered high-dose cyclophosphamide (150 mg/kg) as late intensification. Treatment consisted of induction chemo-radiotherapy, (weeks 1 to 11), consolidation chemotherapy (weeks 11 to 18), and intensification (week 18). Median age was 61.5 years. Eighty-nine percent of patients had a Southwest Oncology Group (SWOG) performance status of 0-1. Twenty-one patients completed all prescribed treatments. There were seven treatment-related deaths, four as a result of intensification. Fifty-six patients are available for response analysis. Thirty-two patients achieved a complete remission (CR) (57%) and fifteen achieved a partial remission (PR) (26%). Median survival for all patients is 11.1 months. Among the 21 patients who received intensification, nine remain alive in a CR with a median survival of 27 months. This sequence of treatments was not associated with a survival advantage for the group as a whole, possibly because of the toxicity of induction and consolidation treatment and the delayed administration of high-dose cyclophosphamide.

Adult↗
PubMed1991

A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study.

Six hundred eighty assessable patients with measureable stage III M1, non-small-cell lung cancer (NSCLC) were randomized to one of five treatment arms including cisplatin, etoposide (VP-16) +/- methylglyoxal bisguanylhydrazone (MGBG; PVp, PVpM); cisplatin, vinblastine (PVe); or PVe alternating with vinblastine, mitomycin (PVeMi); or fluorouracil, vincristine, mitomycin/cyclophosphamide, doxorubicin, cisplatin (FOMi/CAP). The overall response rate was 20% with 3% complete responses and 17% partial remissions. The duration of these responses was not statistically different by treatment regimen and varied from 2.7 months to 5.0 months. The overall median survival for all patients was 5.3 months and is not different by treatment. Toxicity was greater in PVpM. The similarity of results for response, duration of response, and survival does not establish the superiority of any of these platinum-based regimens for standard clinical usage.

Adult↗
PubMed1991

Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience.

We analyzed the 2,531-patient Southwest Oncology Group extensive-stage non-small-cell lung cancer (ENSCLC) data base from 1974 to 1988 to (1) assess the interactions of host- or tumor-related prognostic factors and therapy using Cox modeling and recursive partitioning and amalgamation (RPA) to determine whether each independently predicts outcome, and (2) use RPA to define prognostic subsets with different survival potentials. Good performance status (PS), female sex, and age greater than or equal to 70 years were significant independent predictors in a Cox model applied to the entire population. In a second Cox model for patients with good PS enrolled on recent studies, hemoglobin level greater than or equal to 11.0 g/dL, normal lactate dehydrogenase (LDH), normal calcium, and a single metastatic site were significant favorable factors. The use of cisplatin was an additional independent predictor of improved outcome in both Cox models after adjustments for year of accrual and all prognostic variables. The favorable effect of cisplatin was observed in each of six RPA-derived subgroups from the entire population. A second RPA of 904 patients from recent trials (nearly all received cisplatin-based therapy) resulted in three distinct prognostic subsets based on PS, age, hemoglobin, and LDH; greater than or equal to 1-year survivals were 27%, 16%, and 6% (P less than .0001). The best survival occurred for patients with a good PS who had a hemoglobin level greater than or equal to 11 g/dL and who were older than 47 years. This analysis suggests that although several factors were independent variables in the Cox models, three important prognostic subgroups were easily defined through RPA. Together with other analyses, our results suggest the need to modify the stage IV category in NSCLC.

Adult↗
PubMed1991

Long-term survival and toxicity in small cell lung cancer. Expanded Southwest Oncology Group experience.

The Southwest Oncology Group formed a database of 2,501 patients consecutively enrolled in small cell lung cancer (SCLC) trials since 1976. This report summarizes an analysis of this database to determine predictors of 2- and 5-year survival in limited stage disease (LD) and 1- and 2-year survival in extensive stage disease (ED). In addition, we analyzed the frequency of late recurrences, toxicity, and quality of life issues in the long-term survivors. For consecutive studies, greater than or equal to 2-year survival in LD were 15 percent, 21 percent, 28 percent, and 43 percent; 5-year survivals were 5 percent, 9 percent, 8 percent, and 20 percent. In ED, greater than or equal to 1-year survivals were 27 percent, 23 percent, 21 percent, and 42 percent; greater than or equal to 2-year survivals were 6 percent, 5 percent, 3 percent, and 19 percent. Using the logistic regression multivariate model, independent favorable predictors of 5-year survival for patients accrued to our older LD trials were normal lactate dehydrogenase (LDH) values and good performance status. Therapy as employed in these trials was not an independent factor. However, if patients enrolled on more recent trials were included, 2-year predictors could be assessed. Therapy with concurrent chemoradiotherapy and female gender then became additional independent favorable predictors. In ED, a single metastatic site and a normal LHH value were favorable predictors of survival beyond 1 year. The retrospective review of 63 patients with LD who survived at least 5 years found 33 asymptomatic patients with no recurrent disease; 6 with recurrent SCLC, 3 of whom died; 7 who died of non-cancer-related causes or unknown causes; 3 who died of secondary primary lung cancer; and 14 alive with persistent central nervous system symptoms and signs, possibly due to prophylactic brain radiation as given in the first 3 trials. No increased incidence of this syndrome has yet been observed in subsequent trials. For ED patients, 25 of 51 survivors greater than or equal to 2 years subsequently died of recurrent SCLC. The majority of the long-term survivors with ED (35 of 51) had either a single metastatic site or metastases limited to opposite side of the chest or regional nodes. Our multivariate models support the conclusion that aggressive combined modality, concurrent induction therapy, along with favorable prognostic variables, independently contribute to the improved long-term survival we have observed in LD. Longer follow-up is required to confirm that this improvement has occurred with less late toxicity.

Aged↗
PubMed1990

Chemotherapy for advanced thymoma. Preliminary results of an intergroup study.

OBJECTIVE: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma. DESIGN: Nonrandomized, prospective phase I-II trial. SETTING: A Cooperative Oncology Group trial involving tertiary medical centers. PATIENTS: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response. INTERVENTION: Patients were given cisplatin, 50 mg/m2 body surface area, doxorubicin, 50 mg/m2, and cyclophosphamide, 500 mg/m2, on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m2) was reached. Intravenous hydration with normal saline was administered during treatment courses. For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle. MEASUREMENTS AND MAIN RESULTS: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%). The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years. The median survival time of all eligible patients was 59 months (CI, 22 months to infinity). Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity. CONCLUSIONS: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma. Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma.

Adult↗
PubMed1990

Bone marrow involvement in epithelial ovarian cancer by immunocytochemical assessment.

The incidence of bone marrow involvement with epithelial ovarian cancer has been evaluated as a continuation of interest in autologous bone marrow support. Fifty-eight aspirates were obtained on 50 patients and 53 aspirates were evaluable. Immunocytochemistry with the monoclonal cytokeratin antibodies 35 beta H11 and 34 beta E12 was performed. There have been no complications. Twelve (23%) were positive and three were indeterminate. Stage, grade, and CA-125 level were not different in the two groups. No patient had a positive biopsy at the time of initial diagnosis. The majority of patients were drawn from second-look procedures; of these, 7 of 19 were positive. Five of twelve with positive aspirates died from disease versus 5 of 38 with negative aspirates, and patients with a positive aspirate had a longer overall survival time until death from disease. We can confirm the presence of epithelial ovarian cancer in 23% of patients at varying times in the course of their disease. We cannot identify risk factors for the development of this finding nor the viability of those cells when found in this data set.

Bone Marrow Diseases↗
PubMed1990

Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study.

The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Treatment of small-cell lung cancer with an alternating chemotherapy regimen given at weekly intervals: a Southwest Oncology Group pilot study.

We designed an intensive, weekly treatment regimen for patients with small-cell lung cancer (SCLC) using six of the most active chemotherapeutic agents for this disease (doxorubicin [DOX], cyclophosphamide [CTX], vincristine [VCR], etoposide [VP-16], cisplatin [CDDP], and methotrexate [MTX]). The goal of this program was to gain rapid, repetitive exposure to multiple, active drugs. Treatment was administered weekly for a total of 16 weeks. Seventy-six SCLC patients (limited disease, 34; extensive disease, 42) were treated. The overall complete plus partial response rate was 82%. Complete response rates of 47% and 38% were observed in patients with limited (LD) and extensive disease (ED), respectively. The median survivals for patients with LD and ED were 16.6 and 11.4 months, respectively. Toxicities were tolerable and were primarily hematologic. Twenty-six patients had one or more transient life-threatening toxicities, but only one patient developed a fatal toxicity. Eighty-four percent of the patients received 80% or greater of the intended protocol dosages over the entire 16-week treatment period. We conclude that this intensive, short-duration treatment regimen is at least as good as other "standard" regimens, and we are encouraged aged by the complete response rate and median survival in patients with ED SCLC.

Adult↗
PubMed1990

Determinants of improved outcome in small-cell lung cancer: an analysis of the 2,580-patient Southwest Oncology Group data base.

We analyzed the 2,580-patient Southwest Oncology Group (SWOG) small-cell lung cancer data base from 1976 to 1988 in order to (1) determine the prognostic value of favorable demographic and tumor-related factors and therapy programs using Cox multivariate analyses in limited- and extensive-stage disease (LD, ED), and (2) define patient subgroups with significantly different survivals using recursive partitioning and amalgamation (RPA) analysis to refine the current two-stage system. Cox multivariate models were applied to 1,363 patients in six LD trials: good performance status, female sex, age less than 70 years, white race, and normal lactate dehydrogenase (LDH) were significant favorable independent predictors. Concurrent chemoradiotherapy was also a strong independent predictor of survival. For 1,217 patients in four ED trials, a normal LDH, treatment with an intensive multidrug regimen, and a single metastatic lesion were favorable independent variables in the Cox model. RPA analysis of 1,137 patients in recent LD and ED trials resulted in a regression tree in which the most important prognostic split was LD versus ED. Normal or abnormal LDH, absence or presence of a pleural effusion, and age less than 70 or greater than or equal to 70 years were important in LD, but only LDH was significant in ED. The terminal nodes of the regression tree were amalgamated to form four distinct prognostic subgroups with median survivals of 19.0, 12.5, 10.5, and 6.3 months (P less than .0001). The best survival occurred for younger patients with "true" LD: no effusion and normal LDH. The two intermediate patient subgroups had either LD or ED but still lived significantly longer than those patients with true ED (elevated LDH). This analysis suggests that although several factors were independent prognostic variables in LD in the Cox models, a smaller number of variables can be used to form important prognostic subgroups through RPA. The LDH emerged as a highly significant factor, but performance status and sex did not. A refinement of the current staging system should be made if our results can be confirmed with a combined-group data base analysis.

Adult↗
PubMed1990

Antineoplastic drugs in 1990. A review (Part I).

The drugs used to treat cancer today are a confusing array of compounds with differing origins, mechanisms of action, antitumour spectra, and toxicities. There are 5 chemically distinct types of alkylating agents; the prototypical agent is chlormethine (mustine) and the most recent addition is ifosfamide. Generally these drugs all work in the same fashion and their activity is cell cycle proliferation-dependent but phase-nonspecific. The antimetabolites consist of methotrexate, the pyrimidine and purine analogues, and pentostatin, an adenosine deaminase inhibitor and relative newcomer to the class. The individual mechanisms of action of these agents differ but cytotoxicity is generally cell cycle phase-specific. Naturally occurring antineoplastic agents include the vinca alkaloids, the antitumour antibiotics, 1-asparaginase, the epipodophyllotoxins, and homoharringtonine; it is the most diverse collection of compounds. For these drugs as well as the antimetabolites, the therapeutic and toxic effects often depend heavily on duration of exposure to the drug, an effect known as schedule dependency. Finally, the agents that do not fit one of the above categories are cisplatin (cis-platinum II) and its analogue carboplatin (which is being actively investigated), hydroxycarbamide (hydroxyurea), procarbazine, hexamethylmelamine, amsacrine, and mitoxantrone (mitozantrone). In the future we can expect not only the emergence of new antineoplastic drugs, but also further refinements in the use of existing drugs. We are beginning to understand the various types of resistance manifested by tumour cells. Our ability to use these potent and highly toxic agents safely should continue to improve.

Antineoplastic Agents↗