ABSTRACT
BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.
Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Adult , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Mastectomy, Modified Radical , Neoplasm Recurrence, Local/prevention & control , Premenopause , Radiotherapy/adverse effects , Recurrence , Survival AnalysisABSTRACT
PURPOSE: To determine the maximum-tolerated dose of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) administered biweekly with a fixed dose of cisplatin, to assess the toxicity, and to evaluate the activity of this combination in a phase I/II trial in metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine women with metastatic breast cancer were enrolled; 27 were assessable for response and 29 for toxicity. All but two of the women had received prior adjuvant chemotherapy, with 23 receiving anthracyclines and six previous cisplatin. RESULTS: The initial starting dose of paclitxel 90 mg/m2 and cisplatin 60 mg/m2 became the phase II dose due to dose-limiting neutropenia. Responses were seen in 85% of assessable patients, with three patients (11%) achieving a complete response (CR) and 20 patients (14%) a partial response (PR), for an overall response rate of 85% (95% confidence interval [CI], 66% to 96%). The time to disease progression for patients who achieved a CR was 110 to 200 days, and for those with a PR, it was 96 to 377+ days, with a median time to progression of 7.1 months and a median response duration of 7.9 months. Sites of CR were skin, soft tissue, and lung, and all occurred in women with previous exposure to anthracyclines. Septic events were rare, with two grade 3 infections (7%), only one of which required hospital admission. There were no grade 4 nonhematologic toxicity and minimal grade 3 toxicity. A total of 251 chemotherapy cycles were given -- 16 with paclitaxel alone in five patients. Forty-five percent of patients required dose reductions, while 52% had delays due to neutropenia. CONCLUSION: Biweekly paclitaxel and cisplatin is an active combination in the treatment of metastatic breast cancer, including for patients with previous exposure to anthracyclines.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Cisplatin/administration & dosage , Drug Administration Schedule , Feasibility Studies , Female , Humans , Middle Aged , Paclitaxel/administration & dosage , Treatment OutcomeABSTRACT
A patient with pulmonary metastatic extraskeletal myxoid chondrosarcoma (EMC), of unknown cause, responded dramatically to 16 months of therapy with interferon alfa-2b. This is the first report of a significant response of a patient with EMC to this novel treatment approach.
Subject(s)
Chondrosarcoma/drug therapy , Chondrosarcoma/secondary , Interferon-alpha/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Neoplasms, Unknown Primary , Chondrosarcoma/diagnostic imaging , Humans , Interferon alpha-2 , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Radiography , Recombinant Proteins , Treatment OutcomeABSTRACT
BACKGROUND AND METHODS: We examined the effect of adjuvant systemic therapy on survival after breast cancer among the residents of the Canadian province of British Columbia. Data on survival were collected for all women in whom breast cancer was diagnosed in British Columbia during each of three calendar years chosen to represent different province-wide treatment recommendations: 1974, when no adjuvant systemic therapy was recommended; 1980, when adjuvant chemotherapy was recommended only for premenopausal women with node-positive disease; and 1984, when adjuvant chemotherapy was also recommended for premenopausal women with node-negative disease and lymphatic, vascular, or neural invasion and tamoxifen was recommended for postmenopausal women with involved lymph nodes or lymphatic, vascular, or neural invasion unless their tumors were negative for estrogen receptors. RESULTS: For women less than 50 years of age, disease-specific survival at seven years (i.e., with censoring of data on women who died from causes other than breast cancer) improved from 65.2 to 76.3 percent between 1974 and 1984 (P = 0.008), and overall survival improved from 64.8 to 74.6 percent (P = 0.02). For women from 50 through 89 years of age, disease-specific survival at seven years improved from 62.5 to 70.4 percent between 1980 and 1984 (P = 0.001), and overall survival improved from 53.9 to 58.3 percent (P = 0.05). The timing of the improvements in survival correlated with the introduction of adjuvant systemic therapy in each group. CONCLUSIONS: Survival among women with breast cancer improved significantly in a geographically defined population during the period when adjuvant systemic therapy became widely used.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Cohort Studies , Cyclophosphamide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Methotrexate/administration & dosage , Middle Aged , Retrospective Studies , Survival Rate , Tamoxifen/therapeutic use , Treatment OutcomeABSTRACT
PURPOSE: To establish the optimum biologic dose and maximal-tolerated dose (MTD) of once-daily, subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast (RhuGM-CSF) in patients with breast cancer. PATIENTS AND METHODS: Seventeen patients with either newly diagnosed breast cancer with more than four involved axillary nodes (five patients) or metastatic breast cancer (12 patients) were treated with cyclophosphamide 1 g/m2, doxorubicin 50 mg/m2, and fluorouracil 500 mg/m2 (CAF) intravenously (IV) once every 3 weeks. RhuGM-CSF was administered subcutaneously once daily for 14 days after the second and third CAF cycles, at one of three dose levels. RESULTS: The 125-micrograms/m2/d RhuGM-CSF dose level shortened the duration of neutropenia in only one of three patients. The 250-micrograms/m2/d level was effective in shortening the duration of the neutropenic nadir (< .5 x 10(9)/dL) by 2 or more days in five of six patients. The 500-micrograms/m2/d level caused severe toxicity (chest pain, two patients; deep vein thrombosis, one patient) in three of eight patients. CONCLUSION: RhuGM-CSF administered once daily at the 250-micrograms/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Neutropenia/prevention & control , Adult , Aged , Chemotherapy, Adjuvant , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Female , Fluorouracil/adverse effects , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Humans , Injections, Subcutaneous , Lymphatic Metastasis , Middle Aged , Neutropenia/chemically induced , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Saccharomyces cerevisiaeABSTRACT
Many cancer chemotherapeutic agents can produce toxicity, even at the usual therapeutic doses. Family physicians are often called upon to treat symptoms of these toxicities and to advise patients about them. This brief discussion may help family physicians to anticipate some of the problems, to avoid some, and to manage others more effectively.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Estrogens, Conjugated (USP)/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Methotrexate/administration & dosage , Middle Aged , Tamoxifen/administration & dosageABSTRACT
Fourteen infants in a Neonatal Intensive Care Unit became colonized with Klebsiella pneumoniae. Ten developed septicaemia. All infants survived the acute infection. Details are given of clinical observations and the control measures that were taken.
Subject(s)
Intensive Care Units, Neonatal , Klebsiella Infections/epidemiology , Disease Outbreaks , Female , Humans , Infant, Newborn , Klebsiella pneumoniae , Male , ScotlandABSTRACT
Following complete remission of non-Hodgkin's lymphoma by chemotherapy, irradiation or both, 44 patients were studied to assess the value of bacille Calmette-Guérin (BCG) as maintenance therapy. Patients with stage LI, EI or EII disease were allocated at random to receive BCG or no further maintenance therapy, and those with stage LII, LIII, EIII or IV disease received BCG therapy or orally administered cyclophosphamide. BCG had no effect on the duration of remission or the overall survival from the time of randomization. However, after the first recurrence there was a significant improvement in survival in the patients who had received BCG maintenance therapy.
Subject(s)
BCG Vaccine/therapeutic use , Lymphoma/therapy , Adolescent , Adult , Aged , Clinical Trials as Topic , Humans , Middle Aged , Random Allocation , RecurrenceABSTRACT
Maintenance of remission solely by repeated BCG vaccinations in seven patients with non-Hodgkin's lymphoma who had achieved a complete clinical remission with initial standard therapy has provided sufficient encouragement to begin a randomized clinical trial. In vitro lymphocyte responses to mitogens and PPD used as parameters of cell-mediated immunity have not proved to be of value in predicting early or late recurrence in six pre-trial and trial patients. Eight out of twenty-one patients with malignant melanoma have shown a satisfactory clinical response (10-34 months) to immunotherapy. Those who respond must show immunological reactivity to the stimulating agent, however the best clinical responses were not associated with the highest degrees of in vivo and in vitro sensitization. The skin reactivity and the in vitro lymphocyte response to PPD as well as a 2-3-fold increase in the appearance of colony-forming units in the peripheral blood following the intratumour injection of BCG or PPD are helpful in prognosis and management of these patients. All patients with malignant melanoma who presented with a PHA response less than 40% of normal made a poor response to immunotherapy. Autopsies performed on seven patients dying with extensive melanocarcinomatous disease failed to show any serious adverse toxic reactions or infections from oral and intratumour injections of BCG.
Subject(s)
Lymphoma/therapy , Melanoma/therapy , Administration, Oral , Adult , BCG Vaccine/administration & dosage , Concanavalin A/pharmacology , DNA/biosynthesis , Female , Hematopoietic Stem Cells/immunology , Humans , Immunoglobulins/analysis , Immunotherapy , Injections, Intradermal , Lectins/pharmacology , Lymphocyte Activation/drug effects , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Skin Neoplasms/drug therapy , Tuberculin , Vaccinia virus/immunologyABSTRACT
The clinical findings in 12 patients with an unusual type of leukemia have been reviewed. The leukemic cell cannot be identified with any of the normal hematopoietic cells or with any of the lymphomas and may best be referred to by the descriptive term "hairy cell", which describes its appearance, most clearly seen on phase contrast microscopy. The patients were all males and the major clinical features were enlargement of the liver and spleen, with little lymph node enlargement. Hematologic findings in most patients have been anemia and thrombocytopenia with the characteristic abnormal cells present in the peripheral blood and bone marrow. The disease most often runs an indolent course and has shown little or no response to a variety of forms of treatment.