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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
PubMed2000

Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer.

PURPOSE: Evidence supports the inclusion of the taxanes in the treatment of breast cancer. A recent randomized trial has shown a survival advantage to the addition of paclitaxel in the adjuvant treatment of node-positive patients. Several studies have suggested diminished local control if adjuvant radiation is delayed, while in vitro and in vivo studies have demonstrated a benefit of concurrent administration of taxanes with radiation. For these reasons, we began in 1995 to administer radiation therapy concurrently with the taxanes in advanced breast cancer. This retrospective review examines the feasibility of such treatment. METHODS AND MATERIALS: Forty-four patients were treated with concurrent radiation and either paclitaxel (29 patients) or docetaxel (15 patients). One patient received both paclitaxel and docetaxel. Eighteen patients were treated for recurrent disease, 9 had received prior radiation. Toxicity was assessed by the RTOG scale for acute and late effects. RESULTS: Concurrent radiation and taxane chemotherapy was well tolerated. Nine patients (20%) experienced Grade 3 acute skin toxicity. This was more likely with docetaxel than paclitaxel (p = 0. 04). Among patients undergoing breast conservation, there were no Grade 3 toxicities. With a median follow-up of 11 months, 1 patient has developed breast fibrosis. CONCLUSION: Concurrent administration of both paclitaxel and docetaxel with radiation resulted in acceptable toxicity. Overall, the acute skin toxicity seen with docetaxel was more pronounced. However, among patients undergoing breast conservation the taxanes were both well tolerated. Further study is necessary to assess the impact of concurrent treatment on long-term outcome.

Adult↗
PubMed2000

High-dose busulfan, melphalan and thiotepa as consolidation for non-inflammatory high-risk breast cancer.

The purpose of this study was to evaluate the toxicity and efficacy of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) in patients with high-risk non-inflammatory breast cancer defined as stage II disease > or =10 lymph nodes (n = 52) or stage III (n = 69), and prognostic factors for treatment outcome. One hundred and twenty-one patients (median age, 46 years) were treated with high-dose Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) (HDC) followed by autologous stem cell infusion (ASCI). One hundred patients were initially treated with surgery followed by standard adjuvant chemotherapy prior to HDC/ASCI. Twenty-one patients with stage III disease had inoperable tumors at diagnosis and were treated with neoadjuvant chemotherapy and surgery before HDC/ASCI. Transplant-related mortality was 6%. The probabilities of event-free survival (EFS) at 3 and 5 years (median follow-up of 36 months) from transplant were, for all patients: 0.62-0.60; stage II: 0.71-0.67: stage III: 0.55-0.55 (for stage III adjuvant and neoadjuvant groups: 0.60-0.60 and 0.42-0.42, respectively). Multivariate analysis did not identify variables associated with poor outcome. The efficacy of Bu/Mel/TT is similar to other HDC regimens reported for patients with high-risk non-inflammatory breast cancer. Bu/Mel/TT has high activity in stage II disease and a moderate benefit in stage III operable tumors.

Adult↗
PubMed2000

Factor structure of the Reitan-Indiana Neuropsychological Battery for Children.

The Reitan-Indiana Neuropsychological Battery (RINB) was administered to a sample of children referred for educational and behavioral problems (N = 130). Subtest scores were standardized by age at 1-year intervals (6, 7, and 8 years). A principal components analysis (PCA) with promax rotation of 18 subtest scores produced a five-factor solution. Factor 1 emphasizes tactile/spatial functions, Factor 2 emphasizes concept formation and visual/spatial abilities, Factor 3 reflects motor strength, Factor 4 emphasizes sensory perception, and Factor 5 reflects motor speed. Principal factor analysis (PFA) of these data was performed to permit comparison with the PCA solutions. The PFA and PCA solutions were similar and major conclusions about factor structure were consistent.

Child↗
PubMed1999

Monitoring the response of patients with locally advanced breast carcinoma to neoadjuvant chemotherapy using [technetium 99m]-sestamibi scintimammography.

BACKGROUND: Mammographic and physical examination assessments of the response of locally advanced breast carcinoma (LABC) to neoadjuvant therapy have been shown to be inaccurate. The authors studied the feasibility and accuracy of [technetium 99m]-sestamibi (MIBI) for monitoring the response of patients with LABC to neoadjuvant chemotherapy. METHODS: Patients receiving neoadjuvant chemotherapy for LABC underwent prone lateral scintimammography before therapy, after 2 months of therapy, and close to the completion of chemotherapy (presurgery) if chemotherapy continued for >3 months. Images were analyzed both qualitatively and quantitatively using the lesion-to-normal breast MIBI uptake ratio (L:N). Imaging results were compared with the clinical response and the pathologic response as determined from the posttherapy surgical specimen. RESULTS: A total of 32 patients (29 who were assessable for primary tumor response and 28 who were assessable for lymph node response) were included in the study. The mean change in the primary tumor L:N MIBI uptake ratio after 2 months of chemotherapy was -35% for clinical responders and +17% for nonresponders (P<0.001). Patients achieving a pathologic primary tumor macroscopic complete response (CR) had a mean change in uptake on the presurgical scan of -58% versus -18% for patients with a partial response (P<0.005). A decrease of > or =40% in the MIBI uptake ratio identified CRs with 100% sensitivity and 89% specificity. Pretherapy imaging predicted axillary lymph node metastases in 85% of patients ultimately found to have > or =1 positive lymph nodes at surgery, but was less accurate in identifying residual lymph node disease after therapy (55% sensitivity and 75% specificity). CONCLUSIONS: MIBI imaging accurately assessed the response to neoadjuvant chemotherapy in patients with LABC. Further studies are needed to determine the role of MIBI in this group of patients.

Adult↗
PubMed1999

Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide.

BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. METHODS: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.

Adult↗
PubMed1999

'Neo-FAC' (5-fluorouracil, doxorubicin, and cyclophosphamide) for poor-prognosis stage IV breast cancer: a Southwest Oncology Group Phase II Study.

The authors report a phase II pilot investigation in the Southwest Oncology Group examining a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) incorporating modulated 5-FU in patients with poor-prognosis stage IV breast cancer. Patients with poor-prognosis stage IV breast cancer were treated with this "neo-FAC" as front-line therapy. The regimen consisted of 5-fluorouracil by continuous ambulatory infusion pump at 200 mg/m2/day for 42 days, repeated at 56-day intervals; doxorubicin at 20 mg/m2/week intravenously to a maximum cumulative total dose (including adjuvant therapy, if any) of 500 mg/m2; cyclophosphamide 60 mg/m2/day taken orally; methotrexate 15 mg/m2/week intravenously beginning 1 week after termination of doxorubicin; and oral prednisone decreasing from 60 mg/day on a tapering schedule for a total of 7 weeks of treatment. Treatment was continued until progression, unacceptable toxicity, or patient refusal. Twenty-four patients were accrued to this study. Of these, two were ineligible, and the remaining 22 were evaluable for response. Ten patients experienced grade 3 toxicity, and six had grade 4. There were no treatment-associated deaths. Best responses were a complete response in one patient (5%) and partial responses in 6, for an overall response rate of 32% (7/22 evaluable patients). Overall survival in five pilot studies in the Southwest Oncology Group in this poor-prognosis population are relatively superimposable. The present regimen, with its relatively poor outcome and the expense and inconvenience of administering chemotherapy by ambulatory infusion pump, will not be pursued further.

Adult↗
PubMed1999

Internal consistency of three tests from the Halstead-Reitan neuropsychological battery for older children.

The internal consistency of three neuropsychological tests was examined in a sample of 334 referred children (9-14 years of age). Coefficient alpha was calculated to estimate reliability on the Seashore Rhythm Test (SRT), two forms of the Speech Sounds Perception Test (SSPT), and the Aphasia Screening Test (AST). The standard SSPT appears to have relatively good internal consistency with an average coefficient of.81. The average coefficient for the abbreviated form of the SSPT was considerably lower (i.e.,.73), highlighting the superiority of the standard form in clinical practice. Internal consistency of the SRT was relatively low (i.e.,. 67). This level of reliability may be acceptable in group research and for component tests, but is marginal for independent clinical use. Coefficient alpha for the AST was moderate (i.e.,.77), suggesting adequate reliability for a screening test. These reliability estimates are compared to those obtained in previous studies using these tests in adult samples and with other tests commonly used with children.

Adolescent↗
PubMed1999

Infusional paclitaxel and weekly vinorelbine chemotherapy with concurrent filgrastim for metastatic breast cancer: high complete response rate in a phase I-II study of doxorubicin-treated patients.

PURPOSE: We investigated 96-hour paclitaxel infusion combined with weekly (days eight and 15) vinorelbine as salvage therapy for metastatic breast cancer in anthracycline-exposed patients. All patients received scheduled support with granulocyte colony-stimulating factor (G-CSF; filgrastim). Tumor response, toxicity, time to progression (TTP), and survival were assessed. PATIENTS AND METHODS: This single-center nonrandomized trial enrolled 32 patients. Anthracycline exposure and subsequent progression were common to all patients. Paclitaxel and vinorelbine were escalated over three dosing levels, stratified by liver function. RESULTS: Seven patients (22%) achieved a complete response and nine patients achieved a partial response for an overall response rate of 50%. The median TTP was 6.1 months, and median survival time was 14.1 months. Dose-limiting toxicity was neutropenia, with dose delay or reduction in seven of 32 patients. Febrile neutropenia requiring hospitalization was uncommon (three of 32 patients; 9%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia occurred in two patients (6%), and 13 patients (41%) required RBC transfusions for anemia. Grade 3 nausea and vomiting was seen in one patient, who was found to be Addisonian. Despite potentially overlapping neurologic toxicities of the two agents, only two patients (6%) were removed from the study because of progressive peripheral neuropathy. CONCLUSION: Administration of 96-hour paclitaxel infusion and subsequent weekly vinorelbine with G-CSF support is well tolerated. The response rate, TTP, and survival data are encouraging for therapy given to anthracycline pretreated patients with metastatic breast cancer. If these results can be verified in multi-institution trials, this or a similar combination of drugs would merit investigation as first-line therapy in this patient population.

Adult↗
PubMed1999

Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group.

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Concurrent cisplatin, prolonged oral etoposide, and vincristine plus chest and brain irradiation for limited small cell lung cancer: a phase II study of the Southwest Oncology Group (SWOG-9229).

PURPOSE: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting. METHODS AND MATERIALS: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m2 i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m2 (days 1-14, 29-42, and 57-70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m2 i.v., doxorubicin 50 mg/m2 i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy. RESULTS: Among 56 eligible patients, 93% had SWOG performance status 0-1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimum follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary fibrosis (including one Grade 3) and six cases of pneumonitis (including one Grade 3). CONCLUSION: Concomitant chemoradiation with oral etoposide as part of a platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is not better than our prior best group-wide experience. The progression-free and overall survival are similar to published trials utilizing short-course i.v. etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent advantage to prolonged exposure to etoposide, and toxicity resulted in an inferior therapeutic index compared to programs with shortened exposure.

Administration, Oral↗
PubMed1998

Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study.

PURPOSE: Cisplatin has played a major role in the treatment of non-small-cell lung cancer (NSCLC). This randomized trial was performed by the Southwest Oncology Group (SWOG) to determine whether the combination of vinorelbine and cisplatin has any advantage with regard to response rate, survival, and time to treatment failure over single-agent cisplatin in the treatment of patients with advanced NSCLC. METHODS: Between October 1993 and April 1995, 432 patients with advanced stage NSCLC were randomized to receive arm I (cisplatin 100 mg/m2 every 4 weeks) or arm II (cisplatin 100 mg/m2 every 4 weeks and vinorelbine 25 mg/m2 weekly). All patients were chemotherapy-naive, had performance status (PS) 0 or 1, and had adequate hematologic, renal, and hepatic function. RESULTS: Four hundred fifteen patients were eligible and assessable. On arm I (cisplatin), there was a 12% partial response rate. Arm II (cisplatin and vinorelbine) had a 26% response rate (2% complete responses and 24% partial responses, P = .0002). There was a statistically significant advantage with regard to progression-free survival (median, 2 v 4 months; P = .0001) and overall survival (median, 6 v 8 months; P = .0018) for the cisplatin and vinorelbine arm. One-year survival was 20% for cisplatin alone and 36% for the combination arm. There was more hematologic toxicity on arm II of the study (81% grades 3 and 4 granulocytopenia v 5% on arm I). Other toxicities, such as renal insufficiency, ototoxicity, and nausea and vomiting, and neuropathy were similar. CONCLUSION: The results of this study indicate that the combination of cisplatin and vinorelbine is a superior treatment when compared with single-agent cisplatin in the treatment of advanced NSCLC. Cisplatin and vinorelbine is the new standard for SWOG against which new therapies will be evaluated.

Adult↗
PubMed1998

Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer.

PURPOSE: A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS: Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION: This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.

Aged↗
PubMed1997

Teniposide (VM-26) as a single drug treatment for patients with extensive small cell lung carcinoma: a Phase II study of the Southwest Oncology Group.

BACKGROUND: Teniposide (VM-26) was reported to have activity in small cell lung carcinoma (SCLC). The authors performed a Phase II study of teniposide as a treatment for patients with previously untreated extensive SCLC. METHODS: The study was open to patients with a histologic or cytologic diagnosis of extensive SCLC who had not received prior radiation or chemotherapy. Patients with hematologic values below normal were considered eligible if the impaired bone marrow function was directly attributable to disease involvement. Treatment consisted of teniposide 60 mg/m2 given intravenously (i.v.) on Days 1-5 every 3 weeks. RESULTS: This study opened on September 15, 1988, closed permanently on November 15, 1990, and accrued 45 patients identified at 19 academic, military, and Community Clinical Oncology Program institutions affiliated with the Southwest Oncology Group. Of the 45 registered patients, 41 were eligible. Twenty eight (68%) were males and 13 (32%) were females; the median age was 64 years (minimum, 46 years; maximum, 83 years). Twenty-four patients (59%) had a performance status (PS) on the Zubrod scale of 0-1 and 17 cases (41%) had a PS of 2. Of the 41 eligible patients, 10 had confirmed partial responses (24%) (95% confidence interval, 12-40%). The median survival was 7 months. The significant toxicities noted were Grade 4 leukopenia and/or granulocytopenia, experienced by 15 patients; 1 of these patients also had Grade 4 hyponatremia. One patient died of a respiratory infection. CONCLUSIONS: When administered according to the dosage and schedule selected for this study (60 mg/m2 i.v. on Days 1-5 every 3 weeks), teniposide as a single agent had modest activity in extensive small cell lung carcinoma. The toxicities observed in this study were acceptable.

Actuarial Analysis↗