Showing papers in "Journal of Clinical Oncology in 1995"
TL;DR: High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs, despite severe acute treatment-associated toxicities, and should be considered for initial therapy of patients with appropriately selected metastatic carcinoma.
Abstract: PURPOSETo determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma.PATIENTS AND METHODSTwo hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients.RESULTSThe overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesi...
1,234Â citations
TL;DR: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall and was also possible to decrease therapy for selected patient subsets without compromising survival.
Abstract: PURPOSEThe ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation.PATIENTS AND METHODSOne thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984).RESULTSThe overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine an...
878Â citations
TL;DR: The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery, and this trimodality approach was feasible in this Southwest Oncology Group (SWOG) study.
Abstract: PURPOSETo assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB.PATIENTS AND METHODSBiopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found.RESULTSThe median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were ...
845Â citations
TL;DR: CD34 cell dose is an important predictor of engraftment kinetics after PBSC transplant, regardless of disease or mobilization technique, and the use of postinfusion CSF improves neutrophil recovery, but at low CD34 doses can delay platelet recovery.
Abstract: PURPOSETo analyze factors that affect the collection of peripheral-blood stem cells (PBSC) before transplant and the tempo of engraftment after transplant.PATIENTS AND METHODSA consecutive series of 243 patients with breast cancer (n = 87), malignant lymphoma (n = 90), multiple myeloma (n = 32), or other malignancies (n = 34) had PBSC collected following stimulation with colony-stimulating factors (CSFs) or after chemotherapy followed by CSF. Infusion of PBSC was performed following myeloablative chemotherapy with chemotherapy with or without total-body irradiation (TBI). Postinfusion CSFs were administered to 72 patients. An analysis of factors that influence CD34+ cell yield was performed by linear regression. Cox regression analysis was used to determine factors that affect the kinetics of granulocyte and platelet recovery following infusion of PBSC.RESULTSMobilization with chemotherapy followed by CSF, a diagnosis of breast cancer, absence of marrow disease, no prior history of radiation therapy, and ...
663Â citations
TL;DR: The clinical significance of EML in patients with ANLL treated with modern chemotherapy or bone marrow transplantation is needed and the addition of immunohistochemical stains can assist in preventing such misdiagnoses.
Abstract: PURPOSETo discuss the predisposing risk factor for all forms of extramedullary leukemia (EML) and to review the clinical features, prognostic significance, and treatment strategies for primary EML and leukemia cutis (LC)/granulocytic sarcomas (GS) in the setting of acute nonlymphocytic leukemia (ANLL).METHODSA review of all reports published since 1965 related to all forms of extramedullary leukemia (LC, GS, gingival hypertrophy, and meningeal leukemia [ML]).RESULTSSeveral factors, including chromosomal abnormalities [t(8;21), inv(16)], cell-surface markers (CD56, CD2, CD4, CD7), French-American-British (FAB) subtype (M2, M4, M5), blast differentiation and maturation, patient nutritional status, age, cellular immune dysfunction, high presenting leukocyte count, and decreased blast Auer rods, have been associated with a higher incidence of EML. Of 154 published cases of primary EML identified, 71 (46%) were initially misdiagnosed. The addition of immunohistochemical stains can assist in preventing such mis...
572Â citations
TL;DR: The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial, and this promising combination should be used in investigational trials.
Abstract: PURPOSETo define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy.PATIENTS AND METHODSThirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of > or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles.RESULTSSevere neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 i...
562Â citations
TL;DR: The pharmacokinetic model should prove to be a powerful tool in predicting paclitaxel disposition, regardless of dose and schedule, and should facilitate further pharmacodynamic investigations.
Abstract: PURPOSETo characterize and model the disposition of paclitaxel in humans and define a pharmacodynamic relationships between paclitaxel disposition and its toxicity and efficacy.PATIENTS AND METHODSPaclitaxel pharmacokinetics were studied in 55 courses of therapy in 30 patients. Paclitaxel was administered at 135 mg/m2 or 175 mg/m2 by either a 3- or a 24-hour infusion schedule to patients with advanced ovarian cancer (n = 15), or at 225 mg/m2 by 3-hour infusion to patients with advanced breast cancer (n = 15). Paclitaxel and 6 alpha-hydroxylpaclitaxel were quantified by high-performance liquid chromatography (HPLC). Pharmacokinetics were assessed by noncompartmental and model-dependent methods. Pharmacodynamic correlations were evaluated statistically and by regression models.RESULTSPaclitaxel disposition is nonlinear in humans and, on the 3-hour schedule, 6 alpha-hydroxylpaclitaxel was identified in the plasma of all patients treated. The plasma disposition of paclitaxel and 6 alpha-hydroxylpaclitaxel was...
547Â citations
TL;DR: Cancer patients who participate in phase I trials appear to have an adequate self-perceived knowledge of the risks of investigational agents, however, only a minority of patients appear toHave an adequate understanding of the purpose of phase I Trials as dose-escalation/dose-determination studies.
Abstract: PURPOSEIn an attempt to understand some of the complex issues related to the participation of cancer patients in phase I trials, and the perceptions of patients toward these trials, we conducted a pilot survey study of 30 cancer patients who had given informed consent to participate in a phase I trial at our institution. Concurrently, the oncologists identified by the surveyed patients as responsible for their care were surveyed as well.PATIENTS AND METHODSTwenty-seven of 30 consecutive patients agreed to and completed the survey. Patients were surveyed before they received any investigational agents. Eighteen oncologists participated in this survey study.RESULTSEighty-five percent of patients decided to participate in a phase I trial for reasons of possible therapeutic benefit, 11% because of advice/trust of physicians, and 4% because of family pressures. Ninety-three percent said that they understood all (33%) or most (60%) of the information provided about the trials in which they had decided to partic...
494Â citations
TL;DR: In advanced soft tissue sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared.
Abstract: PURPOSEThe aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas.PATIENTS AND METHODSThis was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C).RESULTSThe overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 ...
492Â citations
TL;DR: The toxicity profile of DOX-SL differs prominently from that of the free drug administered by bolus or rapid infusion and with some differences, resembles that of prolonged continuous infusion.
Abstract: PURPOSEThe purpose of our studies was to define the maximal-tolerated dose of liposomal doxorubicin (DOX-SL; Liposome Technology Inc, Menlo Park, CA), a doxorubicin formulation of polyethyleneglycol-coated liposomes, characterize the toxicities associated with this formulation, and evaluate any indication of antitumor activity within a phase I setting.PATIENTS AND METHODSTwo separate phase I studies were conducted following the initial human pharmacokinetic testing at one of the sites (Hadassah). The starting dose of 20 mg/m2 at the University of Southern California was just below the dose without toxicity in the pharmacokinetic study. At Hadassah, the phase I starting dose was just above their earlier safe single doses, 60 mg/m2. Both studies involved cohorts of at least three patients and redosing every 3 to 4 weeks. To determine the recommended dose for phase II trials, an additional level of 50 mg/m2 every 3 weeks was explored, and the level of 60 mg/m2 every 4 weeks was expanded.RESULTSA total of 56 ...
483Â citations
TL;DR: Attention to the barriers of guidelines development and the sociocultural nature of clinical practice, and respect for clinical experience, can lead to improved strategies for guidelines development.
Abstract: PURPOSETo develop a conceptual tool for the systematic development of cancer treatment practice guidelines.MATERIALS AND METHODSThe guidelines development tool, the Practice Guidelines Development Cycle, was derived from observing an evidence-based practice guidelines initiative at a comprehensive cancer center in Ontario, Canada, and from a literature review that uncovered barriers to guidelines development and implementation. Based on the literature findings and direct observations of how clinicians struggled with evidence-based guidelines development, we evolved a framework to incorporate clinical and administrative factors (eg, costs) into evidence-based guidelines. Use of the Practice Guidelines Development Cycle is illustrated with a clinical example (the use of adjuvant systemic therapy in good-risk, node-negative premenopausal breast cancer patients).RESULTSThe result is the Practice Guidelines Development Cycle, which consists of eight sequential steps, from topic selection to policy formulation....
TL;DR: The majority of the retrospective studies show that angiogenesis is an important new prognostic indicator in early-stage breast carcinoma and this marker should be evaluated in prospective controlled clinical trials to demonstrate whether adjuvant therapies may improve the prognosis of those patients at high risk.
Abstract: PURPOSETo review prognostic and therapeutic applications of angiogenesis research in breast carcinoma.METHODSWe reviewed the (1) biologic role of angiogenesis, particularly in transformation, progression, and metastasis of breast cancer; (2) methods to detect angiogenic activity in human pathology; (3) clinical studies relating clinical outcome of patients with breast cancer to the assessment of angiogenesis; (4) predictive value of angiogenesis for response to anticancer therapies; and (5) pharmacologic characteristics of current antiangiogenic drugs.RESULTSThere is mounting evidence that angiogenesis plays a relevant role in the biologic aggressiveness of breast cancer. Using either immunohistochemical or biochemical methods, several studies have shown a worse prognosis for those patients with tumors with high angiogenic activity. In some studies angiogenesis has an independent prognostic value. The most promising angiogenic inhibitors are under early-phase clinical evaluation in patients with tumors re...
TL;DR: A set of guidelines for breaking bad news that was developed using a consensus process and incorporates the views of medical oncologists, general practitioners, surgeons, nurse consultants, social workers, clergy, human rights representatives, cancer patients, hospital interns, and clinical directors of medical schools in Australia are reported on.
Abstract: PURPOSE AND DESIGN: One of the more difficult tasks that clinicians must perform as part of their care of patients is that of conveying bad news, such as a severe diagnosis or death. However, there is a paucity of empirically founded information that relates to the specific steps for breaking bad news. We report on a set of guidelines for breaking bad news that was developed using a consensus process and incorporates the views of medical oncologists, general practitioners, surgeons, nurse consultants, social workers, clergy, human rights representatives, cancer patients, hospital interns, and clinical directors of medical schools in Australia. RESULTS AND CONCLUSION: It is recommended that further research be undertaken in a number of areas. First, there is a need to assess patients' versus providers' perceptions of the importance of each of the steps in breaking bad news, in order to define criteria for minimal levels of competence in this area. Second, controlled trials are needed to assess the effectiv...
TL;DR: HDR-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.
Abstract: PURPOSEThe aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival.PATIENTS AND METHODSNinety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable.RESULTSThe response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have resp...
TL;DR: The use of tamoxifen has resulted in a substantial modification of breast cancer's natural history, particularly in postmenopausal women, and it appears that the drug's antiproliferative effects are mediated primarily by inhibition of the activities of estrogen through binding to estrogen receptors (ERs).
Abstract: PURPOSEThe mechanisms of antitumor activity, clinical pharmacology, toxicity, and efficacy of tamoxifen in women with early and advanced breast cancer and the drug's potential role in prevention of breast cancer were reviewed.DESIGNA comprehensive review of the literature from 1966 to 1994 was conducted; reports were identified using the Cancerline and Medline data bases.RESULTSThe cellular actions of tamoxifen are not completely understood, but it appears that the drug's antiproliferative effects are mediated primarily by inhibition of the activities of estrogen through binding to estrogen receptors (ERs). Disease-free and overall survival rates have been increased in postmenopausal women with ER-positive tumors when tamoxifen has been used as adjuvant therapy (irrespective of nodal status). In premenopausal women, adjuvant therapy with tamoxifen has been associated with prolongation of disease-free survival, but its impact on survival remains to be defined. Tamoxifen is the initial hormonal treatment of...
TL;DR: Evidence is provided that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaloplatin.
Abstract: PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m2 over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m2), eight (oxaliplatin dose, 800 mg/m2), and 12 (oxaliplatin dose, 1,200 mg/m2) cycles of treatment. RESULTS: At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neu...
TL;DR: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC and high objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy.
Abstract: PURPOSETo determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC).PATIENTS AND METHODSThirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days.RESULTSThirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in...
TL;DR: The EORTC QLQ-C30 seems to yield high test/retest reliability in patients with various cancer diagnoses whose condition is not expected to change during the time of measurement.
Abstract: PURPOSEThe European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated instrument that assesses health-related quality of life (HRQOL) in cancer patients. It is used in cancer clinical trials in Europe, Canada, and the United States, and has demonstrated high reliability and validity in different groups of cancer patients. Despite thorough testing of reliability and validity, we have not identified any reports on its test/retest reliability; thus, a test/retest study was performed at the Norwegian Radium Hospital (NRH).MATERIALS AND METHODSCancer patients from the outpatient clinic who were off treatment for > or = 3 months were eligible for the study. The EORTC QLQ-C30 was given to the patients when they presented for their visit. The second questionnaire was received by the patients 4 days later. Of 291 eligible patients, 270 (93%) agreed to participate and 190 (73%) completed both questionnaires.RESULTSThe test/retest reliability mea...
TL;DR: The analysis confirmed the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of a classical Cox regression model and a RECPAM analysis.
Abstract: Purpose: This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group, Patients and Methods: We included in the analysis all eligible patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working party (ELCWP) during one decode, The patients were treated by chemotherapy regimens based on platinum derivatives. We prospectively collected 23 variables and analyzed them by univariate and multivariate methods. Results: The global estimated median survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks. After univariate analysis, we applied two multivariate statistical techniques. In a Cox regression model, the selected explanatory variables were disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex. These results were confirmed by application of recursive partitioning and amalgamation algorithms (RECPAM), which led to classification of the patients into four homogeneous subgroups. Conclusion: We confirmed by our analysis the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of two methods: a classical Cox regression model and a RECPAM analysis. The classification of patients into the four subgroups we obtained needs to be validated in other series. (C) 1995 by American Society of Clinical Oncology.
TL;DR: A multimarker PCR assay is more reliable and sensitive than a single-marker assay for detection of melanoma cells in blood of patients and can provide important insight into tumor progression kinetics without major surgical or conventional radiologic diagnostic procedures.
Abstract: PURPOSEThe objective of the study was to develop a sensitive multimarker polymerase chain reaction (PCR) assay to detect circulating melanoma cells in patient blood. The rationale was that malignant melanoma is heterogeneous in regards to antigen expression.PATIENTS AND METHODSA PCR assay that uses four melanoma-associated gene markers (tyrosinase, p97, MUC18, and MAGE-3) was developed. Sensitivity and specificity of the PCR assay for individual markers were assessed using 10 melanoma cell lines and peripheral-blood lymphocytes (PBL) from 39 normal volunteers as controls. The assay's sensitivity and specificity were improved using nested primers and Southern blot analysis. Patients (N = 119) with American Joint Committee on Cancer (AJCC) stages I to IV disease were evaluated for circulating melanoma cells using the four gene markers under optimal conditions.RESULTSAll melanoma-associated gene markers were expressed in at least 80% of the melanoma lines, whereas 37 of 39 normal PBL tested negative for all ...
TL;DR: The single-agent infusion regimens demonstrated the most encouraging results with a favorable toxicity profile and a 2-month longer survival duration than 5-FU bolus therapy.
Abstract: PURPOSEA variety of fluorinated pyrimidine-based regimens for the treatment of disseminated colorectal cancer have been presented in the medical literature. The Southwest Oncology Group designed a screening trial of seven regimens of fluorouracil (5-FU) to assess efficacy and toxicity afforded by biochemical modulation or schedule variations.PATIENTS AND METHODSSix hundred twenty patients were entered into this trial between August 1989 and January 1993. Eligible patients were classified as having recurrent or disseminated disease that was measurable or nonmeasurable. All eligible patients were evaluated for toxicity and survival; patients with measurable disease were evaluated for response according to standard criteria.RESULTSNo regimen achieved a higher response rate than single-agent bolus 5-FU. Eighty-four percent of patients have been monitored until death. The median survival time for the entire cohort is 14 months. Survival hazards ratios showed a positive trend in favor of the unmodulated infusio...
TL;DR: F fluorouracil plus levamisole is tolerable and accepted as standard surgical adjuvant therapy for patients with stage III colon cancer, but the data from this study in stage II patients suggest a decreased relapse rate without a significant improvement in survival.
Abstract: PURPOSETo determine the effectiveness of fluorouracil plus levamisole administered postoperatively to patients with resected stage II (Dukes' B2) colon cancer.PATIENTS AND METHODSThis randomized controlled clinical trial (INT-0035) was performed by National Cancer Institute-sponsored cancer clinical trials cooperative groups. Patients were assigned to observation only or to fluorouracil (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side effects were assessed.RESULTSThree hundred eighteen eligible patients were analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole reduced the recurrence rate by 31%, although this trend was not statistically significant (P = .10). A total of 87 patients died: 43 on observation and 44 on fluorouracil plus levamisole. Disparity between effects on recurrence rate and o...
TL;DR: This trial is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy, and such neoadjuvant treatment cannot be recommended outside of a clinical trial.
Abstract: PURPOSETo evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer.PATIENTS AND METHODSPatients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery.RESULTSOf 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgica...
TL;DR: Acitretin 30 mg/d over 6 months had significantly more effect than placebo in the prevention of squamous cell carcinomas and reduced the occurrence of keratotic skin lesions in a group of renal transplant recipients with severe lesions.
Abstract: PURPOSEThe purpose of this study was to investigate the effect of acitretin on the development of keratotic skin lesions, and on squamous cell carcinomas and basal cell carcinomas in a group of renal transplant recipients.PATIENTS AND METHODSForty-four renal transplant recipients with more than 10 keratotic skin lesions on the hands and forearms were enrolled onto a randomized, double-blind, placebo-controlled trial to test the possible skin cancer-preventing effect of a 6-month treatment with acitretin 30 mg/d.RESULTSNo deterioration in renal function occurred in any of the 38 assessable patients treated. During the 6-month treatment period, two of 19 patients (11%) in the acitretin group reported a total of two new squamous cell carcinomas, compared with nine of 19 patients (47%) in the placebo group who developed a total of 18 new carcinomas (chi 2 = 6.27, P = .01). The relative decrease in the number of keratotic skin lesions in the acitretin group was 13.4%, as compared with a relative increase in th...
TL;DR: Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence, with improvement in survival with new treatments most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.
Abstract: PURPOSETo examine outcome of treatment for patients with recurrent follicular lymphoma.PATIENTS AND METHODSTwo hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued.RESULTSThe overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor b...
TL;DR: In view of the single-agent activity seen in advanced breast cancer, modest toxicity profile, and novel mechanism of action, gemcitabine deserves evaluation in breast cancer and is an ideal candidate for combination therapy.
Abstract: PURPOSEIn this phase II study, the efficacy and tolerability of gemcitabine were studied in 44 patients with locally advanced or metastatic breast cancer.PATIENTS AND METHODSOf 40 patients assessable for response, 14 were chemotherapy-naive, seven had received adjuvant chemotherapy, and 19 had received one prior chemotherapy regimen for metastatic disease. Gemcitabine was administered as a 30-minute intravenous infusion once a week for 3 weeks followed by a 1-week rest every 4 weeks. The mean number of completed cycles administered was 2.7 and the mean dosage delivered was 725 mg/m2 per injection. Eighty-one percent of doses were delivered as scheduled.RESULTSThere were three complete responses and seven partial responses, for an overall response rate of 25.0% (95% confidence interval [CI], 12.7% to 41.2%). Four patients were not assessable for efficacy (one had insufficient therapy, two had no bidimensionally measurable disease, and one had neither). All responses were independently validated by an exter...
TL;DR: Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.
Abstract: PURPOSEThe purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone.PATIENTS AND METHODSDocetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen.RESULTSObjective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxici...
TL;DR: In this paper, the authors evaluated the activity and toxicity of combination paclitaxel and carboplatin in advanced non-small-cell lung cancer (NSCLC) patients.
Abstract: PURPOSETo determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC).PATIENTS AND METHODSEligibility required measurable disease (stage IV or stage IIIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count > or = 2,000/microL, platelet count > or = 100,000/microL serum creatinine concentration < or = 1.5 mg/dL, and bilirubin level < or = 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m2/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repe...
TL;DR: There is no benefit to the treatment of high-grade astrocytomas in children with eight-drugs-in-1-day chemotherapy compared with CCNU, vincristine, and prednisone, and a difference in toxicity between the two chemotherapeutic regimens.
Abstract: PURPOSEIn a previous randomized trial, the addition of adjuvant chemotherapy to postoperative radiotherapy proved beneficial in the treatment of childhood high-grade astrocytomas. The present study tests the hypothesis that an eight-drug adjuvant chemotherapy regimen would improve survival in such children compared with the three-drug regimen of the prior study.PATIENTS AND METHODSBetween April 1985 and May 1990, patients between the ages of 18 months and 21 years with newly diagnosed high-grade astrocytomas were eligible for this study, as determined by the treating institution's histopathologic diagnosis. Treatment consisted of postoperative local-field radiotherapy and adjuvant chemotherapy, either lomustine (CCNU), vincristine, and prednisone (control regimen) or eight-drugs-in-1-day chemotherapy (experimental regimen). Two cycles of postoperative preirradiation chemotherapy were administered in the experimental regimen. Patients were evaluated radiographically every 3 months after irradiation.RESULTS...
TL;DR: Patients with ER+/c-erbB-2+ metastatic breast cancer are less likely to respond to hormone treatment than ER-/progesterone receptor-positive (PR+) patients and their survival duration is shorter.
Abstract: PURPOSEDecisions concerning the use of hormone therapy to treat metastatic breast cancer are made on the basis of the presence of estrogen receptor (ER). Despite the presence of ER, half of patients will not respond to hormone treatment. The purpose of this study was to determine the effect of overexpression of HER-2/neu on the response to hormone therapy.PATIENTS AND METHODSSera from 300 metastatic breast cancer patients with ER-positive (ER+), ER status unknown, or ER-/progesterone receptor-positive (PR+) randomized to receive second-line hormone therapy with either megestrol acetate or fadrozole were evaluated. An enzyme immunoassay (EIA) specific for the extracellular domain of the c-erbB-2 (HER-2/neu) oncogene product was used to detect serum levels.RESULTSFifty-eight patients (19.3%) had elevated serum c-erbB-2 protein levels, using a selected cut-point of 30 U/mL. The response rate (complete responses [CRs] plus partial responses [PRs] plus stable disease [S]) to endocrine therapy was 40.9% in 242 ...