The cancer journal from Scientific American最新文献

Purpose: This study evaluated the feasibility, when given in the community, of dose-dense, sequential ATC (doxorubicin, paclitaxel, cyclophosphamide) as adjuvant therapy for breast cancer with four or more metastatic axillary lymph nodes.

Patients and methods: Patients were recruited after definitive breast cancer surgery if four or more axillary nodes were involved by metastatic cancer and if distant metastases were not present on computed tomographic scan or bone scan. Forty patients received doxorubicin, 90 mg/m2 every 14 days for three cycles; paclitaxel, 250 mg/m2 every 14 days for three cycles; and cyclophosphamide, 3 g/m2 every 14 days for three cycles with filgrastim support. Chemotherapy was administered by the referring physician.

Results: Mean dose intensity was 99% for doxorubicin, 96% for paclitaxel, and 99% for cyclophosphamide. Grade 3 toxicities included mucositis (13%), nausea/vomiting (10%), neuropathy (13%), and myalgia/arthralgia (10%). Thirteen patients had neutropenic fever. One patient developed acute leukemia. Three relapses have occurred. Ninety percent of patients are alive and disease-free at a median follow-up of 24 months.

Discussion: ATC can be administered in the community at full doses with acceptable toxicity. Preliminary efficacy data suggest that this high-dose, intensively scheduled regimen warrants comparison with standard therapy for high-risk patients.

Purpose: This phase II multi-institutional trial of the Southwest Oncology Group was designed to evaluate the efficacy and toxicity of docetaxel in chemotherapy-naive patients with extensive-stage small cell lung cancer.

Patients and methods: Forty-seven patients with extensive-stage small cell lung cancer were entered onto the study. Treatment consisted of docetaxel, 100 mg/m2, as a 1-hour intravenous infusion repeated every 21 days, with protocol-specified dose reductions for toxicity.

Results: Forty-three patients were eligible. A total of 158 cycles of docetaxel were administered (median, three cycles; range, one to nine). Ten patients (23%) (95% confidence interval, 12% to 39%) achieved partial responses. The median progression-free and overall survivals were 3 and 9 months, respectively. Therapy was generally well tolerated. Grade 4 neutropenia occurred in 58% of patients. Febrile neutropenia developed in five patients (12%), and infection was documented in 14% of patients. There was one treatment-related death caused by pneumonia in a patient who had developed bilateral pneumothoraces. Other toxicities (grade 3/4) included malaise, fatigue, and lethargy (21%); nausea (19%); stomatitis (14%); edema (9%); and sensory neuropathy (9%).

Discussion: Docetaxel, at a dose of 100 mg/m2, is an active agent in the treatment of small cell lung cancer. Reversible neutropenia is the most common toxicity associated with this treatment. The overall survival (9 months) with this agent is comparable to that reported with other new chemotherapeutic agents in small cell lung cancer and warrants additional evaluation of docetaxel in combination therapy.

Purpose: Epithelial ovarian cancer is the fourth leading cause of cancer-related death in women. Five-year survival is about 25%, and new approaches to the treatment of this disease are dearly warranted. This study was designed to determine the feasibility of using an in vitro assay for drug resistance to guide treatment after cytoreductive surgery. We present preliminary results of this study after a median follow-up of 24 months.

Materials and methods: We treated 66 patients with advanced ovarian cancer by use of a combination of cytoreductive surgery and chemotherapy. Patient inclusion criteria included histologic confirmation of epithelial ovarian cancer, International Federation of Gynecology and Obstectrics (FIGO) stage III, no prior chemotherapy or radiation therapy, no coexisting neoplasm, and optimal residual disease (< 2 cm). Malignant tissue from the involved ovary of each patient was tested in vitro for drug resistance, and chemotherapy was directed individually by assay results. On the basis of the assay we treated 19 patients with platinum/paclitaxel (TP) and 47 with platinum/cyclophosphamide (CP).

Results: Three-year survival (Kaplan-Meier estimate) was 69%; the 95% confidence interval was 58% to 80%. There was no difference in 3-year survival between the 19 patients treated with TP (66%) and the 47 patients treated with CP (74%). The cost-effectiveness of each treatment option was determined. It cost $4615 to achieve 3-year survival for patients receiving CP and $17,988 to obtain a similar survival with TP. The cost-effectiveness of assay-directed therapy was $9768.

Discussion: Because of the high recurrence rate and the poor long-term survival of women with advanced ovarian cancer, improved therapies for this disease are needed. After surgical debulking, we used results of an in vitro assay for drug resistance to individually select chemotherapy for the patients in this study. Although the 3-year survival of 69% obtained in the present study appears good compared with previously published studies of optimally debulked patients, the results must be viewed with caution. Patients were not randomized, and differences in prognostic factors, such as tumor grade, patient age, and performance status, could account in part for the higher survival found in the current study compared with previously published studies. Treatment with either CP or TP resulted in equivalent 3-year survival. The cost to achieve 3-year survival with this protocol, including the cost of the drug resistance assay, was $9768. We believe that consideration of costs avoided by the elimination of ineffective treatments, needless toxicity, and loss of quality of life would likely increase the cost-effectiveness of assay-directed therapy compared with conventional therapy. This study demonstrates that it is feasible to use an in vitro assay in routine clinical practice to eliminate

Treatment of a 48-year-old woman with advanced cervical cancer with the synthetic vitamin A derivative, 9-cis retinoic acid (9cRA), resulted in thyroid-stimulating hormone suppression without clinical evidence of thyrotoxicosis, which resolved spontaneously when the drug was withdrawn. 9cRA, which is a pan-retinoid (RAR and RXR) agonist, has previously been implicated in induction of interactions between the thyroid receptor and the retinoid receptor, RXR, with endocrine target organ specificity. Furthermore, 9cRA has been shown to down-regulate thyroid-stimulating hormone messenger RNA in a pituitary-specific fashion in a murine model, a finding consistent with the pituitary-restricted thyrotoxicosis observed in our patient. This is the first reported case of thyroid-stimulating hormone suppression by 9cRA and suggests that patients receiving this agent should be monitored for pituitary and thyroid function abnormalities.

Purpose: Paclitaxel has emerged as one of the most active anticancer agents in clinical oncology. Hypersensitivity reactions encountered in the clinical development of this drug prompted the implementation of premedication regimens and prolonged infusions, later amended to a 3-hour infusion schedule. Now that paclitaxel is frequently used in outpatient therapy, optimum efficiency in delivery is an issue. A 1-hour drug infusion is more efficient for both the patient and the clinic staff and can help reduce administration costs. This article reviews the current experience with 1-hour paclitaxel infusions.

Methods: Published studies using 1-hour paclitaxel infusions, including weekly studies, trials of combination chemotherapy, and combined-modality studies, were reviewed. Studies were evaluated for both efficacy and toxicity.

Results and conclusions: Paclitaxel administered by 1-hour infusion as part of weekly or every-3-week treatment regimens is active in a variety of tumors, including breast, ovarian, and lung cancer and carcinoma of unknown primary site. Leukopenia, the most common serious toxicity, is usually manageable without hematopoietic growth factor support. The frequency of neurotoxicity appears comparable for 1-hour and 3-hour regimens, and there is no increased risk of hypersensitivity reactions. Infusion duration has been suggested to be an important predictor of response in some tumor types. Evaluation of this issue using a 1-hour paclitaxel infusion as reference is reasonable. One-hour infusions of paclitaxel should simplify outpatient administration, reduce administration costs, and reduce clinic time for patients. Practical information regarding administration of paclitaxel by 1-hour infusion is provided.

Purpose: To conduct a retrospective analysis of chemotherapy and radiation sequencing in lymph node-negative breast cancer patients treated with breast-conserving surgery.

Patients and methods: Between February 1982 and January 1996, 124 patients with lymph node-negative breast cancer underwent breast-conserving surgery with axillary dissection followed by chemotherapy and radiation therapy. The outcome of 68 patients who received chemotherapy first was compared with that of 56 patients who received radiation first. The two groups were balanced with respect to patient age, tumor stage, margin status, and estrogen and progesterone receptor status. Sixty-two percent of the patients had T1 primary disease. The median follow-up among surviving patients was 44 months for the chemotherapy-first group and 61 months for the radiation-first group.

Results: There were no statistically significant differences in local control, disease-free survival, or overall survival between the two groups. Five-year actuarial rates for local control for the chemotherapy-first and the radiation-first groups were 100% and 94%, respectively. Five-year recurrence-free rates for the chemotherapy-first and radiation-first groups were 92% and 77%, respectively. The 5-year overall survival rate was 89% for both groups.

Discussion: Giving chemotherapy before radiation in lymph node-negative breast cancer did not compromise local control. Given the concerns about increased distant metastases if radiation is given first, the chemotherapy-radiation sequence is recommended.