Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Doxorubicin is considered among the most active single agents used against advanced breast cancer. Recent advances in the design of liposomes as carriers of cytotoxic drugs have resulted in a new formulation of doxorubicin with improved pharmacokinetic and tumor-localizing properties. The objectives of this dose-escalating pilot study were to evaluate the efficacy and safety of the sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) for the treatment of metastatic breast cancer. Lipo-Dox was given at the dosage of 45 mg/m2 over 1 hr of intravenous infusion every 4 weeks initially and could be escalated up to a maximum of 60 mg/m2. Response was assessable in 17 of 19 intent-to-treat patients. An objective response was achieved in 41.2% (95% confidence interval: 17.8%-64.6%) of patients (5.9% complete response and 35.3% partial response), and 23.5% had stable disease. Median time to disease progression was 163 days. Major treatment-related toxicities included neutropenia, stomatitis, and skin toxicity in this dose-escalation program. Impressively, no grade 4 toxicities have ever been observed. The only grade 3 nonhematological toxicity ever to occur was reversible skin toxicity, presented as palmar-plantar erythrodysthesia. No severe nausea/vomiting, wig-necessary alopecia, or significant cardiac function change were encountered. In conclusion, Lipo-Dox is shown by this first reported pilot study to be an active agent for treatment of advanced breast cancer with a safety profile that differs markedly from free doxorubicin. The dosage of 45-60 mg/m2 every 4 weeks was well tolerated. Because myelosuppression and other nonhematological toxicities associated with Lipo-Dox were generally mild and acceptable, further assessment of this drug particularly in combination with other chemotherapeutic drugs in the management of early or advanced breast cancer is suggested.
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PMID:A dose-escalating pilot study of sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) in patients with metastatic breast cancer. 1473 1

A systematic review was performed to determine whether first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation improves response rate, time-to-disease progression, or survival compared with standard-dose chemotherapy in patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. The MEDLINE, EMBASE, and Cochrane Library databases were searched. Three randomized trials (2 phase 3, 1 phase 2), 12 phase 2, and 5 phase 1 dose-escalation trials were located. One randomized trial (N=314) did not detect significant differences in response rate (P=.65) or survival (log-rank P=.98) between high-dose doxorubicin plus ifosfamide with granulocyte macrophage colony-stimulating factor and doxorubicin plus ifosfamide at standard doses. Progression-free survival, however, was significantly longer in the high-dose arm (log-rank P=.03). Higher rates of thrombocytopenia, infection, grade 3 of 4 asthenia, and stomatitis were observed with high-dose compared with standard-dose chemotherapy. Preliminary results from a second randomized trial (N=162) indicated no benefit with respect to tumor response for an intensified mesna, doxorubicin (Adriamycin), ifosfamide, and dacarbazine regimen with granulocyte colony-stimulating factor support compared with standard doxorubicin, ifosfamide, and dacarbazine. Grade 4 thrombocytopenia was significantly higher with the high-dose regimen. Four phase 2 trials of high-dose regimens observed tumor response rates greater than 50%. Phase 1 trials reported dose-limiting toxicity for dose-intensive chemotherapy regimens. On the basis of the available evidence, high-dose chemotherapy with growth factor or autologous bone marrow/stem cell transplantation should not be used in the routine treatment of patients with inoperable, locally advanced, or metastatic soft tissue sarcoma.
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PMID:Dose-intensive chemotherapy with growth factor or autologous bone marrow/stem cell transplant support in first-line treatment of advanced or metastatic adult soft tissue sarcoma: a systematic review. 1822 66


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