Seminars in oncology
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Seminars in oncology · Dec 2003
ReviewEfficacy and safety of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy for non-Hodgkin's lymphoma.
Radioimmunotherapy, an emerging treatment option for certain patients with non-Hodgkin's lymphoma (NHL), enables the targeting of cytotoxic radiation to tumor cells with minimal irradiation of normal cells. Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was approved in February 2002 for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including patients with rituximab-refractory NHL. ⋯ The results of clinical trials show that (90)Y ibritumomab tiuxetan can be used effectively and safely in many patients with NHL, including those with mild thrombocytopenia and those with disease that is refractory to rituximab, without the adverse events associated with conventional chemotherapy and external beam radiation therapy. The use of (90)Y ibritumomab tiuxetan does not preclude subsequent therapy with other conventional treatment options.
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Seminars in oncology · Dec 2003
Clinical TrialClinical trial of endorectal amifostine for radioprotection in patients with prostate cancer: rationale and early results.
Tolerance of the normal rectal mucosa to radiation injury limits the dose that can be safely delivered to the prostate gland with definitive external beam radiation therapy. The radioprotective agent amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD) is approved for intravenous use. Laboratory studies indicate that rectal administration results in preferential accumulation of amifostine in the rectal mucosa, and in clinical studies, neither free parent compound nor free active metabolite has been detected in the systemic circulation. ⋯ Daily endorectal administration was well tolerated. To date, six patients have experienced grade 2 (Radiation Therapy Oncology Group) acute toxicities, all but one because of frequent bowel movements relieved by loperamide. The initial trial will proceed until 18 patients are accrued, at which time an interval evaluation of both early and late toxicity endpoints will be conducted.
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Seminars in oncology · Dec 2003
Randomized Controlled Trial Clinical TrialAmifostine reduces radiochemotherapy-induced toxicities in patients with locally advanced non-small cell lung cancer.
Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small cell lung cancer, but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), a radioprotector, could reduce the incidence of RCT-induced acute and late toxicities. Between October 1997 and August 1999, 73 patients with previously untreated stage IIIa-IIIb non-small cell lung cancer were randomized to treatment with RCT alone or RCT plus amifostine (300 mg/m(2) daily intravenous infusion). ⋯ Endoscopic grade >or= 2 esophagitis was observed in eight of 15 patients in the RCT group and in three of 18 patients in the RCT plus amifostine group (P =.061). No significant differences in response rates were noted between patients receiving RCT with or without amifostine (P =.498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced non-small cell lung cancer without compromising antitumor efficacy.
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Trastuzumab has had a major impact in the treatment of HER2-positive metastatic breast cancer. In combination with chemotherapy, trastuzumab provides significant clinical benefit in terms of increased response rate and extended survival compared with chemotherapy alone in patients with HER2-positive advanced breast cancer. Trastuzumab also has therapeutic activity as monotherapy in the front-line management of HER2-overexpressed or HER2-amplified metastatic breast cancer. ⋯ In this review, the design of the four major phase III multicenter adjuvant trastuzumab trials will be described and their major differences highlighted. Because therapy with trastuzumab has been associated with cardiac toxicity, especially with prior or concurrent anthracyclines, the evaluation of cardiac dysfunction in the adjuvant trial setting is also a priority. For now, the use of trastuzumab as adjuvant therapy is still investigational, but its integration has tremendous potential to improve treatment outcomes in patients with primary breast cancer.
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Seminars in oncology · Aug 2003
ReviewAntisense strategies targeting protein kinase C: preclinical and clinical development.
Altered protein kinase C-alpha (PKC-alpha) expression has been implicated in tumor promotion and carcinogenesis. One potentially attractive therapeutic intervention may be the use of selective antisense oligonucleotides to inhibit production of PKC-alpha. ⋯ Data from phase I and II studies have led to ongoing randomized phase III trials in combination with either cisplatin and gemcitabine or carboplatin and paclitaxel. Studies in other tumor types will also investigate the benefit of combining LY900003 with conventional chemotherapy.