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1.
AIDS Care ; 18(4): 332-8, 2006 May.
Article in English | MEDLINE | ID: mdl-16809110

ABSTRACT

Sustained virological suppression requires adherence to >95% of doses of therapy. Overall there is paucity of data on adherence interventions among women and post-intervention outcomes. In this pilot study, we evaluated a novel strategy of weekly delivery of medications (Directly Delivered Therapy: DDT) for six months using an outreach worker (ORW), among ARV naïve indigent women starting HAART and compared the 'during intervention' and 'post-intervention' outcomes to the health care team (a nurse educator, a case worker, a pharmacist and social worker/drug addictions counsellor) based approach termed Adherence Coordination Services (ACS) and the Standard of Care (SoC) historical referent group. The baseline characteristics of the three groups were comparable. The proportion of women who achieved sustained virologic suppression in 4-8 month period for DDT; ACS and SoC groups were 86% (18/21); 54% (6/11); and 36% (8/22) (P<0.004); and in the 10-14 month period were 80% (12/15); 54% (6/11) and 45%(10/22) (P=0.036 for DDT vs. SoC). Retention rate in the DDT was 87%, and 92% of 307 ORW visits were kept, and post-intervention satisfaction was high. Short-term weekly delivery of medications using a community based liaison is a feasible, acceptable and a cost-effective strategy for improving both short-term and perhaps long-term adherence among women initiating their first HAART regimen.


Subject(s)
Antiretroviral Therapy, Highly Active , Cognitive Behavioral Therapy/methods , HIV Infections/therapy , Adult , Community Health Services , Female , Humans , Patient Acceptance of Health Care/statistics & numerical data , Patient Compliance , Pilot Projects , Texas , Treatment Outcome
2.
J Clin Oncol ; 23(24): 5542-51, 2005 Aug 20.
Article in English | MEDLINE | ID: mdl-16110015

ABSTRACT

PURPOSE: This randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS AND METHODS: Patients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent. RESULTS: In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time. CONCLUSION: Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Paclitaxel/therapeutic use , Taxoids/therapeutic use , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Chi-Square Distribution , Disease Progression , Docetaxel , Female , Humans , Infusions, Intravenous , Logistic Models , Middle Aged , Proportional Hazards Models , Quality of Life , Treatment Outcome
3.
Ann Oncol ; 12(9): 1259-64, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11697837

ABSTRACT

BACKGROUND: Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer. PATIENTS AND METHODS: Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks. RESULTS: Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Paclitaxel/analogs & derivatives , Taxoids , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Deoxycytidine/administration & dosage , Docetaxel , Female , Humans , Infusions, Intravenous , Middle Aged , Neoplasm Metastasis , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Survival Analysis , Treatment Outcome , Gemcitabine
4.
Pediatrics ; 107(4): E51, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11335772

ABSTRACT

BACKGROUND: Pediatric residents need the knowledge and physical examination skills to evaluate common musculoskeletal injuries. The ankle and the knee are the 2 most common sites of musculoskeletal injury in young athletes. Methods for evaluating pediatric residents' knowledge and skills in examining the ankle and knee are needed. OBJECTIVES: 1) To describe the development of a method for evaluating pediatric residents' knowledge and skill in performing physical examinations of the ankle and knee, and 2) to report the reliability of this method. METHODS: A written test and a Clinical Skills Assessment Examination (CSAE) with a rating index were developed by the investigators to evaluate pediatric residents' knowledge and skills in examining the ankle and knee. Fifty-eight pediatric residents completed the written test and examined the ankle and knee of one standardized patient at the beginning of a required 1-month adolescent medicine rotation. Forty-eight residents repeated the evaluation at the end of the month. The investigators rated the residents' performance of the CSAE and then assessed interrater reliability using Cronbach's alpha. Test-retest correlation was calculated to assess the reliability of the written test. RESULTS: Test-retest correlation for the written test was 0.72, establishing its reliability. Interrater reliability for rating the CSAE of the ankle and knee was 0.98 and 0.90, respectively. CONCLUSION: Pediatric residents' knowledge and skills in examining the ankle and knee can be reliably evaluated using the written test and CSAE described in this article. These could be used to assess the effectiveness of current curricula in improving pediatric residents' knowledge and skill in evaluating ankle and knee complaints and to assist in the design of future curricula. musculoskeletal, evaluation methods, resident curriculum.


Subject(s)
Ankle Injuries/diagnosis , Educational Measurement/methods , Internship and Residency , Knee Injuries/diagnosis , Pediatrics/education , Physical Examination/methods , Adolescent Medicine/education , Clinical Competence/standards , Educational Measurement/statistics & numerical data , Humans , Internship and Residency/methods , Internship and Residency/statistics & numerical data , Physical Examination/standards , Reproducibility of Results , Sports Medicine/education , Teaching/methods , Teaching/statistics & numerical data
5.
Pediatrics ; 107(4): E52, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11335773

ABSTRACT

BACKGROUND: Pediatric residents have the need for additional training in the care of common musculoskeletal injuries. OBJECTIVES: To implement and evaluate the effects of a teaching intervention on pediatric residents' knowledge and skills in performing the physical examination of the ankle and knee. STUDY DESIGN: Prospective, intervention, single-sample study design. METHODS: Pediatric residents (n = 58) on a 1-month adolescent medicine rotation received a teaching intervention after a baseline evaluation of their knowledge and skills. The teaching intervention was designed to improve their knowledge about and skills in performing physical examinations of the ankle and knee. The intervention included watching a videotape, followed by observation of the attending physician demonstrating the techniques on a standardized patient, followed by correct demonstration of the techniques by the resident. The residents' knowledge and skills were assessed at the end of the rotation and 9 months later. Knowledge was assessed using a written examination. Skills assessment was performed using a Clinical Skills Assessment Examination. RESULTS: At baseline, the residents performed 37% of the ankle and 18% of the knee physical examination techniques correctly. At 1 and 9 months, the residents' knowledge of ankle and knee examinations was greater than at baseline. The residents performed 77% of the techniques correctly at 1 month and 67% at 9 months. The residents performed 55% of the knee examination techniques correctly at 1 month and 47% at 9 months. The teaching intervention was rated highly by the residents. CONCLUSIONS: The residents' performance of ankle and knee examinations was suboptimal at baseline and improved significantly after the teaching intervention. Observed improvements persisted for a mean of 35 weeks. The teaching intervention described in this study could meet the need for improved ankle and knee examination skills, the 2 most common sites of skeletal injury in young athletes. The teaching model is novel in that it couples videotape and skills-based teaching methods with reliable evaluation methods. This model teaching method could be adapted for use in other pediatric residency training programs and other content areas. musculoskeletal, physical examination, resident curriculum.


Subject(s)
Ankle Injuries/diagnosis , Educational Measurement/methods , Internship and Residency/statistics & numerical data , Knee Injuries/diagnosis , Pediatrics/education , Physical Examination/methods , Teaching , Adolescent Medicine/education , Clinical Competence/standards , Curriculum , Educational Measurement/statistics & numerical data , Humans , Internship and Residency/standards , Physical Examination/standards , Prospective Studies , Remedial Teaching/methods , Sports Medicine/education
6.
J Clin Oncol ; 19(6): 1750-8, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11251006

ABSTRACT

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m(2), day 1), or regimen B, cisplatin (100 mg/m(2), day 1) plus vinorelbine (25 mg/m(2), days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 x 10(12) particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examined in posttreatment tumor biopsies using reverse transcriptase polymerase chain reaction. RESULTS: There was no difference between the response rate of lesions treated with p53 gene therapy in addition to chemotherapy (52% objective responses) and lesions treated with chemotherapy alone (48% objective responses). Subgroup analysis according to the chemotherapy regimens revealed evidence for increased mean local tumor regressions in response to additional p53 gene therapy in patients receiving regimen B, but not in patients receiving regimen A. There was no survival difference between the two chemotherapy regimens, and the median survival of the cohort was 10.5 months (1-year survival, 44%). Transgene expression was confirmed in tumor samples from 68% of patients, and toxicities attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral adenoviral p53 gene therapy appears to provide no additional benefit in patients receiving an effective first-line chemotherapy for advanced NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Genes, p53/genetics , Genetic Therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Adenoviridae/genetics , Adult , Aged , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Disease Progression , Female , Genetic Vectors , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Survival Analysis , Treatment Outcome
7.
Ann Oncol ; 12(1): 89-94, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11249055

ABSTRACT

BACKGROUND: Docetaxel and gemcitabine are active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in NSCLC patients failing one prior regimen. PATIENTS AND METHODS: Forty patients were enrolled. Prior chemotherapy was a platinum-based combination in 36 patients, using vinorelbine in 26 patients and etoposide in 10 patients. The other four patients had prior single agents. Tumors were refractory or resistant to front-line therapy in 80% of patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/m2 day 1, with cycles repeated every four weeks. RESULTS: Thirteen patients responded (32.5%; 95% confidence interval (CI): 19%-49%), including one complete and 12 partial responses. Responses were observed at all metastatic sites, with similar response frequencies in platinum-sensitive and platinum-resistant/refractory tumors. The median time to progression for responders was nine months, with two responses lasting longer than a year. Median survival was 8.1 months. Hematologic toxicities included grade 4 neutropenia in 23 patients, with 4 episodes of febrile neutropenia, grade 3-4 thrombocytopenia in 9 patients, and anemia requiring red cell transfusions in 9 patients. With the exception of asthenia, severe non-hematologic toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, is an active and safe second-line therapy for NSCLC patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Adult , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Docetaxel , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Survival Analysis , Treatment Outcome , Gemcitabine
9.
Am J Health Promot ; 14(5): 292-300, 2000.
Article in English | MEDLINE | ID: mdl-11009855

ABSTRACT

PURPOSE: This study examined breast and cervical cancer knowledge, attitudes, and screening behaviors among different Hispanic populations in the United States. DESIGN: Data were collected from a random digit dial telephone survey of 8903 Hispanic adults from eight U.S. sites. Across sites, the average response rate was 83%. SETTING: Data were collected as part of the baseline assessment in a national Hispanic cancer control and prevention intervention study. SUBJECTS: Analysis was restricted to 2239 Hispanic women age 40 and older who were self-identified as either Central American (n = 174), Cuban (n = 279), Mexican American (n = 1550), or Puerto Rican (n = 236). MEASURES: A bilingual survey instrument was used to solicit information on age, education, income, health insurance coverage, language use, U.S.-born status, knowledge of screening guidelines, attitudes toward cancer, and screening participation. Differences in knowledge and attitudes across Hispanic groups were assessed by either chi-square tests or analysis of variance. Logistic regression models assessed the influence of knowledge and attitudes on screening participation. RESULTS: The level of knowledge of guidelines ranged from 58.3% (Mexican Americans) to 71.8% (Cubans) for mammography, and from 41.1% (Puerto Ricans) to 55.6% (Cubans) for Pap smear among the different Hispanic populations. Attitudes also varied, with Mexican Americans and Puerto Ricans having more negative or fatalistic views of cancer than Cuban or Central Americans. Knowledge was significantly related to age, education, income, language preference, and recent screening history. Overall, attitudes were not predictive of mammography and Pap smear behavior. CONCLUSIONS: Factors related to mammography and Pap smear screening vary among the different Hispanic populations. Limitations include the cross-sectional nature of the study, self-reported measures of screening, and the limited assessment of attitudes. The data and diversity of Hispanic groups reinforce the position that ethno-regional characteristics should be clarified and addressed in cancer screening promotion efforts. The practical relationships among knowledge, attitudes, and cancer screening are not altogether clear and require further research.


Subject(s)
Attitude to Health/ethnology , Breast Neoplasms/prevention & control , Hispanic or Latino/psychology , Mammography/statistics & numerical data , Papanicolaou Test , Uterine Cervical Neoplasms/prevention & control , Vaginal Smears/statistics & numerical data , Adult , Breast Neoplasms/ethnology , Female , Health Behavior , Health Care Surveys , Health Expenditures , Health Knowledge, Attitudes, Practice , Hispanic or Latino/statistics & numerical data , Humans , Middle Aged , Socioeconomic Factors , United States , Uterine Cervical Neoplasms/ethnology
10.
Clin Lung Cancer ; 1 Suppl 1: S20-3, 2000 Apr.
Article in English | MEDLINE | ID: mdl-14725738

ABSTRACT

Both docetaxel and gemcitabine are active against chemotherapy-pretreated non small-cell lung cancer (NSCLC). We previously demonstrated that weekly gemcitabine can be safely combined with monthly docetaxel with promising antineoplastic activity. In a recently completed phase II trial, 38 NSCLC patients failing upfront chemotherapy were treated with gemcitabine 800 mg/m2 on days 1, 8, and 15 and docetaxel 100 mg/m2 on day 1 every 4 weeks. The intent-to-treat response rate was 33% (95% CI: 19%-55%), with one complete and 11 confirmed partial responses. Responses were seen at all disease sites and in 31% of patients refractory to front-line chemotherapy. The median time to disease progression for the responders was 8 months, and two have remained progression-free for longer than a year. Hematological toxicities included grade 4 neutropenia in half of patients, febrile neutropenia in 10%, and grade 3-4 thrombocytopenia in 25%. The most prominent nonhematological toxicity was asthenia. We conclude that this doublet is active and safe, producing durable responses at all disease sites and in patients with platinum-refractory NSCLC.

11.
J Clin Oncol ; 17(11): 3374-88, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10550131

ABSTRACT

PURPOSE: In 1989, the National Surgical Adjuvant Breast and Bowel Project initiated the B-22 trial to determine whether intensifying or intensifying and increasing the total dose of cyclophosphamide in a doxorubicin-cyclophosphamide combination would benefit women with primary breast cancer and positive axillary nodes. B-25 was initiated to determine whether further intensifying and increasing the cyclophosphamide dose would yield more favorable results. PATIENTS AND METHODS: Patients (n = 2,548) were randomly assigned to three groups. The dose and intensity of doxorubicin were similar in all groups. Group 1 received four courses, ie, double the dose and intensity of cyclophosphamide given in the B-22 standard therapy group; group 2 received the same dose of cyclophosphamide as in group 1, administered in two courses (intensified); group 3 received double the dose of cyclophosphamide (intensified and increased) given in group 1. All patients received recombinant human granulocyte colony-stimulating factor. Life-table estimates were used to determine disease-free survival (DFS) and overall survival. RESULTS: No significant difference was observed in DFS (P =.20), distant DFS (P =.31), or survival (P =.76) among the three groups. At 5 years, the DFS in groups 1 and 2 (61% v 64%, respectively; P =. 29) was similar to but slightly lower than that in group 3 (61% v 66%, respectively; P = 08). Survival in group 1 was concordant with that in groups 2 (78% v 77%, respectively; P =.71) and 3 (78% v 79%, respectively; P =.86). Grade 4 toxicity was 20%, 34%, and 49% in groups 1, 2, and 3, respectively. Severe infection and septic episodes increased in group 3. The decrease in the amount and intensity of cyclophosphamide and delays in therapy were greatest in courses 3 and 4 in group 3. The incidence of acute myeloid leukemia increased in all groups. CONCLUSION: Because intensifying and increasing cyclophosphamide two or four times that given in standard clinical practice did not substantively improve outcome, such therapy should be reserved for the clinical trial setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Life Tables , Mastectomy, Radical , Middle Aged , Treatment Failure
12.
Ann Oncol ; 10(8): 989-91, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10509164

ABSTRACT

PURPOSE: To evaluate the efficacy of a novel multiday schedule of vinorelbine and displatin in patients with advanced NSCLC. PATIENTS AND METHODS: Thirty patients were enrolled, including 27 patients with stage IV disease, and 11 patients with performance status of 2. They received a maximum of four chemotherapy cycles with cisplatin 20 mg/m2/day and vinorelbine 15 mg/m2/day intravenously (i.v.) for four consecutive days, every three weeks, with prophylactic filgrastim. RESULTS: Sixteen patients responded (53%, 95% confidence interval (95% CI): 34%-72%), including two complete and fourteen partial confirmed responses. Median survival for all patients was 8.1 months, with actuarial one-year and two-year survival rates of 40% and 15%. Despite prophylactic filgrastim, the delivered vinorelbine dose intensity of 16.8 mg/m2/week caused febrile neutropenia in 48% of patients (16% of cycles), resulting in one treatment-related death. Common nonhematologic toxicities included delayed emesis, asthenia, and constipation. CONCLUSIONS: This multiday vinorelbine-cisplatin schedule is highly active against advanced NSCLC but results in frequent neutropenic complications. The myelotoxicity and antitumor efficacy of vinorelbine in NSCLC patients may be schedule-dependent.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Confidence Intervals , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Severity of Illness Index , Survival Rate , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
13.
J Clin Oncol ; 16(12): 3866-73, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9850032

ABSTRACT

PURPOSE: To determine the maximum-tolerated dose of monthly docetaxel combined with fixed-dose weekly gemcitabine and describe the dose-limiting toxicities (DLTs) of the combination. PATIENTS AND METHODS: Patients with refractory solid tumors were treated with gemcitabine days 1, 8, and 15 every 4 weeks at a fixed dose of 800 mg/m2. Two docetaxel administration schedules were studied, with the drug administered either day 1 or day 15 at doses of 45, 60, 75, and 100 mg/m2 per cycle. RESULTS: Forty patients received 132 cycles of chemotherapy. On the day-1 schedule, the maximum-tolerated docetaxel dose was the highest planned dose of 100 mg/m2 with two DLT episodes among 12 patients treated with 34 cycles at this dose level. On the day-15 schedule, delivery of the planned docetaxel doses was not feasible because of thrombocytopenia and hepatic dysfunction. Hematologic toxicities included grade 4 neutropenia in 16 patients, with three episodes of febrile neutropenia; grades 3 to 4 thrombocytopenia in nine patients; and anemia that required RBC transfusions in 10 patients. For patients treated at the highest docetaxel dose level, myelosuppression was not dose limiting and only one of 34 cycles was complicated by febrile neutropenia. The most common nonhematologic toxicities were asthenia, flu-like symptoms, and fluid retention. Antineoplastic activity was noteworthy, with partial responses in nine of 21 patients with pretreated non-small-cell lung cancer (NSCLC; 43%; 95% confidence interval, 22 to 66), in four of seven patients with breast cancer, and in one patient with esophageal adenocarcinoma. CONCLUSION: Gemcitabine 800 mg/m2 days 1,8, and 15 can be safely combined with docetaxel 100 mg/m2 day 1 of a 28-day cycle. The observed antitumor activity warrants phase II evaluation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Taxoids , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Docetaxel , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/analogs & derivatives , Treatment Outcome , Gemcitabine
14.
Brain Res ; 798(1-2): 320-4, 1998 Jul 06.
Article in English | MEDLINE | ID: mdl-9666158

ABSTRACT

The effects of intrathecal pretreatment with aminophylline on intrathecal norepinephrine-produced or serotonin-produced suppression of noxiously evoked discharges in thalamic parafascicular neurons were investigated in 35 urethane-anesthetized rats. The results showed that: (1) both intrathecal norepinephrine (15 nmol) or serotonin (20 nmol) produced significant suppression of noxiously evoked discharges in parafascicular neurons; (2) intrathecal aminophylline (120 nmol) blocked the norepinephrine-produced suppression of noxiously evoked discharges, while the same dose of aminophylline exhibited no significant effect on the serotonin-produced suppression of these discharges in parafascicular neurons. The results suggest that spinal norepinephrine-produced, but not serotonin-produced, antinociceptive effects may be mediated by adenosine as one of successive chemical links in the spinal dorsal horn circuitry.


Subject(s)
Adenosine/pharmacology , Neurons/physiology , Nociceptors/drug effects , Norepinephrine/administration & dosage , Thalamus/physiology , Aminophylline/administration & dosage , Aminophylline/pharmacology , Animals , Electrophysiology , Female , Injections, Spinal , Male , Norepinephrine/pharmacology , Rats , Rats, Sprague-Dawley , Serotonin/administration & dosage , Serotonin/pharmacology , Thalamus/cytology
15.
Int J Radiat Oncol Biol Phys ; 40(5): 1039-47, 1998 Mar 15.
Article in English | MEDLINE | ID: mdl-9539558

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/radiotherapy , Cranial Irradiation , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Administration, Oral , Adult , Aged , Carcinoma, Small Cell/mortality , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Survival Analysis , Vincristine/administration & dosage
16.
Life Sci ; 62(11): PL143-8, 1998.
Article in English | MEDLINE | ID: mdl-9515562

ABSTRACT

The effects of intrathecally (i.t.) administered GABA(A)-receptor antagonist picrotoxin or bicuculline on the antinociception produced by i.t. serotonin (5-HT), gamma-aminobutyric acid (GABA), muscimol--the GABA(A) agonist or baclofen--the GABA(B) agonist were investigated and compared using the tail-flick assay in rats. The results showed that 1) both i.t. picrotoxin (1.5 nmol) and i.t. bicuculline (0.5 nmol) exhibited a partial and later-emerged blockade on the antinociception produced by 5-HT (120 nmol) or GABA (1.5 nmol); 2) both i.t. picrotoxin and i.t. bicuculline, with the same dosages, completely blocked the antinociception produced by muscimol (1.0 nmol), but showed no effects on that produced by baclofen (0.3 nmol). The results suggest that GABA may mediate the 5-HT-induced antinociception at the spinal level, with the GABA(B)-receptors exhibiting the effect at the early-stage and the GABA(A)-receptors at the later stage of the 5-HT-induced antinociception.


Subject(s)
Analgesics/pharmacology , Receptors, GABA/physiology , Serotonin/pharmacology , Spinal Cord/drug effects , Analgesics/administration & dosage , Analgesics/antagonists & inhibitors , Animals , Baclofen/antagonists & inhibitors , Baclofen/pharmacology , Bicuculline/administration & dosage , Bicuculline/pharmacology , Female , GABA Agonists/administration & dosage , GABA Agonists/pharmacology , GABA Antagonists/administration & dosage , GABA Antagonists/pharmacology , Injections, Intraventricular , Male , Muscimol/administration & dosage , Muscimol/antagonists & inhibitors , Muscimol/pharmacology , Picrotoxin/administration & dosage , Picrotoxin/pharmacology , Rats , Rats, Wistar , Receptors, GABA/classification , Receptors, GABA/drug effects , Serotonin/administration & dosage , Spinal Cord/physiopathology , gamma-Aminobutyric Acid/administration & dosage , gamma-Aminobutyric Acid/pharmacology
17.
J Clin Oncol ; 16(2): 589-92, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9469346

ABSTRACT

PURPOSE: Topotecan is a topoisomerase I inhibitor with antitumor activity against hematologic and solid tumor malignancies. We evaluated its activity in refractory and relapsing multiple myeloma patients who had received one prior chemotherapeutic regimen. PATIENTS AND METHODS: Toptecan 1.25 mg/m2/d was administered as a 30-minute infusion for 5 days repeated every 3 weeks. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d subcutaneously was administered after the first course of treatment if neutropenia was dose-limiting. RESULTS: Forty-six patients entered the study, with 43 patients eligible. The major toxicity was granulocytopenia with grade 3 or better occurring in 40 of 43 patients treated; 21 of 43 patients developed grade 3 or greater thrombocytopenia. Other significant toxicity included mild nausea in 23 patients and mild vomiting in 13 patients. The overall response rate (partial response or better) was 16% (95% confidence interval, 7% to 31%), with responses occurring in both relapsed and refractory patients. Responses have lasted 70 to 477+ days, with a median progression-free survival duration of 13 months and median survival time of 28 months. CONCLUSION: Topotecan has activity in refractory and relapsing multiple myeloma. Future investigation of topotecan in multiple myeloma including combination therapy and the study of other topoismerase I inhibitors is warranted.


Subject(s)
Antineoplastic Agents/therapeutic use , Multiple Myeloma/drug therapy , Topotecan/therapeutic use , Adult , Aged , Antineoplastic Agents/adverse effects , Drug Resistance, Neoplasm , Female , Humans , Male , Middle Aged , Multiple Myeloma/mortality , Recurrence , Survival Rate , Topotecan/adverse effects
18.
Cancer ; 80(6): 1029-33, 1997 Sep 15.
Article in English | MEDLINE | ID: mdl-9305702

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Teniposide/therapeutic use , Actuarial Analysis , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/adverse effects , Female , Humans , Male , Middle Aged , Survival Analysis , Treatment Outcome
19.
Cancer ; 78(10): 2070-7, 1996 Nov 15.
Article in English | MEDLINE | ID: mdl-8918399

ABSTRACT

BACKGROUND: In patients with advanced esophageal adenocarcinoma, the efficacy and palliative role of systemic chemotherapy are not well defined. The primary objective of this Phase II trial was to evaluate the antitumor activity and toxicity of a multiday chemotherapy schedule of high dose cisplatin and etoposide in patients with unresectable or metastatic esophageal adenocarcinoma. A secondary objective was to assess the efficacy of this regimen in palliating dysphagia. METHODS: Twenty-seven eligible patients with unresectable locoregional or metastatic esophageal adenocarcinoma were treated with cisplatin, 30 mg/m2/day, and etoposide, 60 mg/m2/day, intravenously daily for 5 days, every 3 weeks. After three cycles of chemotherapy, all patients were assessed for response. Patients with responding metastatic disease were given one additional cycle of chemotherapy, and patients with locoregional disease received radiation and concurrent continuous infusion of 5-fluorouracil at 300 mg/m2/day for the duration of radiation therapy. Patients were questioned about dysphagia symptoms initially and then weekly during chemotherapy. RESULTS: The major toxicities included myelosuppression, nausea and vomiting, and peripheral sensory neuropathy, with one treatment-related death. Major responses were observed in 13 patients (48%; 95% confidence intervals, 36-74%), including 5 complete and 8 partial responses. Dysphagia relief occurred in 89% of 18 symptomatic patients within a median time of 16 days. The median survival duration for all patients was 9.8 months, and the actuarial 3-year survival rate was 22%. CONCLUSIONS: Multiday chemotherapy with high dose cisplatin and etoposide is active in patients with advanced esophageal adenocarcinoma. Toxicities associated with this regimen are substantial but manageable.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Male , Middle Aged , Palliative Care , Survival Rate
20.
Ann Thorac Surg ; 62(4): 1005-9; discussion 1009-10, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8823080

ABSTRACT

BACKGROUND: We wanted to determine factors affecting survival rates of benefits to, and complications in patients with esophageal cancer treated with photodynamic therapy. METHODS: From 1982 to January 1994, we used photodynamic therapy to treat 77 patients with esophageal carcinoma and evaluated survival to July 1994. All patients had failed, refused, or were ineligible for surgical intervention, ionizing radiation therapy, or chemotherapy. RESULTS: The only significant variable affecting survival was clinical stage. Median survival after photodynamic therapy was as follows: all patients, 6.3 months (mean survival, 9.2 months); stage I, not reached; stage II, 12 months; stage III, 6.2 months; and stage IV, 3.5 months. For stages III and IV, a Karnofsky performance status of 70 or higher had a significant effect. For stage III, the median survival was 6.3 months when the Karnofsky performance status was equal to or greater than 70 and 3.5 months when it was less than 70. For stage IV, the median survival was 5.5 months when the Karnofsky performance status was equal to or greater than 70 and 2.5 months when it was lower than 70. Seven stage I patients with no treatment prior to photodynamic therapy had an estimated 5-year survival rate of 62%. Three patients with stage I invasive adenocarcinoma and Barrett's mucosa diagnosed when they underwent endoscopy for dysphagia were alive with no evidence of disease 17, 44, and 59 months after photodynamic therapy. CONCLUSIONS: Photodynamic therapy for esophageal carcinoma caused minimal complications and no procedure-related deaths. Photodynamic therapy can be considered an alternative treatment for patients with Barrett's esophagus with severe dysplasia or patients with stage I carcinoma who are under consideration for operation but are high surgical risks. The length of palliation for patients having "noncurative" treatment was equal to or better than that reported historically for most other treatment regimens.


Subject(s)
Adenocarcinoma/drug therapy , Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Photochemotherapy , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Esophageal Neoplasms/mortality , Female , Humans , Male , Middle Aged , Photochemotherapy/adverse effects , Prospective Studies , Survival Rate
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