Seminars in oncology
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Seminars in oncology · Aug 2001
Randomized Controlled Trial Clinical TrialPrevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted two sequential randomized clinical trials to aid in resolving uncertainty about the treatment of women with small, localized, mammographically detected ductal carcinoma in situ (DCIS). After removal of the tumor and normal breast tissue so that specimen margins were histologically tumor-free (lumpectomy), 818 patients in the B-17 trial were randomly assigned to receive either radiation therapy to the ipsilateral breast or no radiation therapy. B-24, the second study, which involved 1,804 women, tested the hypothesis that, in DCIS patients with or without positive tumor specimen margins, lumpectomy, radiation, and tamoxifen (TAM) would be more effective than lumpectomy, radiation, and placebo in preventing invasive and noninvasive ipsilateral breast tumor recurrences (IBTRs), contralateral breast tumors (CBTs), and tumors at metastatic sites. ⋯ Thus, if it is accepted from the P-1 findings that women at increased risk for invasive cancer are candidates for an intervention such as TAM, then it would seem that women with a history of DCIS should also be considered for such therapy in addition to radiation therapy. That statement does not imply that, as a result of the findings presented here, all DCIS patients should receive radiation and TAM. It does suggest, however, that, in the treatment of DCIS, the appropriate use of current and better therapeutic agents that become available could diminish the significance of breast cancer as a public health problem.
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Seminars in oncology · Aug 2001
ReviewEuropean perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown high clinical antitumor activity in several tumor types, including ovarian, breast, and lung carcinoma. Preclinical studies have shown that paclitaxel has an additive effect when combined with platinum compounds. Early clinical trials confirmed these data and established the dose range for both drugs. ⋯ In this trial, paclitaxel/cisplatin is delivered before etoposide/cisplatin and concurrent radiotherapy followed by surgery in locally advanced non-small cell lung cancer. Preclinical studies underline the radiosensitizing effect of paclitaxel, and many clinical studies are being conducted with radiotherapy in association with paclitaxel alone or in combination with platinum compounds. The use of paclitaxel in regimens without platinum and in triplet combinations is also being studied, and the optimal manner in which to administer this active agent clearly is of interest.
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Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors. Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents. Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.
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Despite aggressive treatment, the high-grade malignant glioma (specifically, anaplastic astrocytoma and glioblastoma multiforme) have a poor prognosis with current methods. Relapse is nearly universal, responses in recurrent disease are not enduring, and quality of life because of tumor growth is poor. New treatment strategies that address symptom control and quality of life as well as progression-free and overall survival are urgently needed. ⋯ Additionally, patients receiving temozolomide had superior responses in all seven quality-of-life domains tested, which included the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire functions and brain-cancer-specific symptoms. A large, multicenter, single-arm trial (N = 162) showed an impressive response rate for patients with relapsed anaplastic astrocytoma receiving temozolomide, and patients maintained or improved their quality of life compared with baseline values. For patients with recurrent malignant glioma, temozolomide provides a therapeutic option with a predictable safety profile, clinical efficacy, and convenient dosing that can provide important quality-of-life benefits.
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Seminars in oncology · Aug 2001
ReviewDoxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects.
Investigation of the combination of the taxanes with doxorubicin in the treatment of breast cancer has logically progressed, with the ultimate goal of identifying a safe and effective regimen for use in the adjuvant setting. Initial phase II findings of the concurrent doxorubicin/paclitaxel combination resulted in substantial response rates, but at a high cost. A much higher percentage of patients than expected developed anthracycline-induced cardiomyopathy. ⋯ Ongoing studies are underway to assess the role of the doxorubicin/docetaxel combination in the adjuvant setting as primary chemotherapy in the neoadjuvant setting. It is here that the most benefit on survival of breast cancer patients is likely to be shown. At the same time, it is in the adjuvant setting where the absence of potentially late cardiac and other toxicities must be assured.