Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
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PMID:A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer. 754 29

Although chemotherapy is considered the cornerstone of treatment for small cell lung cancer (SCLC), the majority of SCLC patients relapse and die of their disease within 2 years of diagnosis. Until newer, more effective drugs are developed, both optimization of available chemotherapeutic regimens and the use of combined chemotherapy/radiotherapy will be required to improve the survival of SCLC patients. Combining ifosfamide, carboplatin, and etoposide, among the most active single agents against SCLC, into the ICE regimen was a logical move that has resulted in improved response and survival rates. In limited and extensive SCLC, respectively, ICE and ICE administered with vincristine (VICE) have achieved overall response rates of 79% to 94% and 77% to 100% and 2-year survival rates of 24% to 33% and 9% to 25%, respectively. Treatment-related toxicities, especially myelosuppression, have hindered efforts to accelerate the administration of ICE and VICE regimens and to incorporate them into combined-modality treatments. However, the use of hematologic support measures, including growth factors and peripheral blood progenitor cells, may pave the way for maximizing the effectiveness of these regimens.
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PMID:Chemotherapy with vincristine/ifosfamide/carboplatin/etoposide in small cell lung cancer. 761 Mar 97

Many antineoplastic drugs and cytotoxic irradiation induce apoptosis in cancer cells. ICE and ICE-like proteases play important roles in drug-induced apoptosis of cancer cells. We evaluated the cellular factors affecting susceptibility to apoptosis using gene-transfected cells. Introduction of bcl 2 gene into human small cell lung cancer cells conferred resistance to mitomycin C and irinotecan. DNA fragmentation was reduced in these cells. These results indicate apoptosis is one of the mechanisms of cell death caused by some antineoplastic drugs. Investigations are ongoing to elucidate the contribution of the Bcl 2 family proteins to antineoplastic drug induced apoptosis. Wild type p53-transfected cancer cells were sensitive to anticancer drugs. On the other hand, p53-depleted cells were reported to be more sensitive to taxanes than p53-proficient cells. Introduction of Rb gene and p16-gene enhanced cytotoxicity of taxanes and topoisomerase I inhibitors, respectively. In clinical studies, patients of non small cell lung cancer with high expression of Bcl-2 were reported to show longer survival than patients with lower expression. However, this result may be confusing because Bcl-2 reduced the efficacy of antineoplastic drugs. Further evaluation is required to determine the cellular proteins serving as markers for treatment efficacy or prognosis.
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PMID:[Apoptosis and chemosensitivity]. 903 Feb 34

A total of 30 with good prognosis small cell lung cancer were treated with a modified 'ICE' (ifosfamide, carboplatin and etoposide) chemotherapy regimen in an attempt to achieve a high response rate with less toxicity than is seen with the full 'ICE' regimen. This was given every 4 weeks for a maximum of six cycles. In total 25 patients (83%, 95% CI (70-97%)) experienced a partial or complete response at some stage of their treatment. Of these patients, 12 (40%, 95% CI (22-58%)) showed a complete response. A total of 19 patients (63%) had to have their dose reduced and/or delayed at some point due to toxicity. Nadir blood counts showed that 19 patients (63%, 95% CI (46-81%)) had WHO grade 3 or 4 thrombocytopenia, and 24 (86%, 95% CI (73-99%)) had grade 3 or 4 neutropenia. A total of 17 patients (53%) completed six cycles of chemotherapy. In total 3 patients died during treatment all due to treatment-related complications. Median survival was 12.6 months (95% CI (11.6, 14.7 months)). Nausea, vomiting, dysphagia, activity, mood and overall condition, as recorded using daily diary cards, were worse at the beginning of each chemotherapy cycle. Both response rates and survival were clinically acceptable. However, neutropenia and thrombocytopenia, although reduced from rates reported with the full ICE regimen, were still high. A prospective randomised controlled trial is now needed to assess this regimen in more detail.
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PMID:Modified ice study: a phase II study of an intensive, modified ICE regimen (ifosfamide, carboplatin and etoposide) in patients with better prognosis, small cell lung cancer. 982 45

We have evaluated the combination of ifosfamide, carboplatin and etoposide (ICE regimen) along with mesna in 26 previously untreated patients with non small cell lung cancer (NSCLC). Thirteen stage III B and 13 stage IV patients received intermediate doses of ifosfamide (1000 mg/m2), carboplatin (120 mg/m2) and etoposide (120 mg/m2) given intravenously on day 1 to 3 every 4 weeks. Except for one patient who experienced grade 3 transient thrombocytopenia no major events of hematological or systemic toxicity were observed. Response rate (27%, 95% C.I., 10 to 44%), median duration of response (9 months, range 6-15), and survival (9.5 months, range 2-44+) were comparable to those achieved with conventional cisplatin-containing regimens. Our ICE combination, as compared to standard or high dose schedules appears effective, safe, well tolerated, and devoid of severe hematological toxicity.
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PMID:Phase II study with ifosfamide, carboplatin, etoposide (ICE regimen) at intermediate dosage for advanced non small cell lung cancer (NSCLC). 987 59

Intensive chemotherapy combined with chest radiation may ameliorate survival in small cell lung cancer (SCLC). In a prospective study, we treated 18 patients with limited SCLC with an intensive sequential single agent (ifosfamide, carboplatin, etoposide and paclitaxel, (ICE-T)) chemotherapy with the support of unprocessed stem-cell enriched whole blood and G-CSF and concomitant bi-fractionated chest radiotherapy (60 Gy). The treatment was delivered in a short time of 10 weeks. The results were compared with an historical patient group treated with six cycles of standard chemotherapy of etoposide and cisplatin and concomitant chest radiotherapy. After a 3-year median follow up, the 2-year progression free (PFS) and overall survival (OS) are 54 and 63% in the ICE-T group, respectively. In the control group, median PFS and OS were 13 and 17 months and the 2-year PFS and OS were 32% (P=0.20) and 47% (P=0.25), respectively. This short and intensive chemo-radiotherapy regimen is well tolerated and induces promising survival results. The use of stem cell enriched whole blood should be investigated in larger randomized studies.
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PMID:Intensive chemotherapy with whole blood stem-cell support and concurrent chest radiotherapy in small cell lung cancer: a phase I/II trial. 1200 45

Small cell lung cancer (SCLC) is highly sensitive both to radiotherapy and chemotherapy. Given its high chemo sensitivity, even two decades ago, SCLC was one of the first malignancies deemed suitable for maximising the dose and dose intensity with the support of autologous bone marrow (ABMT). On the whole, results were disappointing and the procedure was practically abandoned. Nowadays some interest is again emerging due to improvements in supportive care, such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC). Data of 505 patients included in 26 studies were reviewed. About two thirds of these patients had LD (limited disease). Late intensification protocols were used in 311 patients who, however, represented only the 30% of the population initially given conventional chemotherapy. Of the patients not achieving complete remission (CR) after induction, high-dose induced a CR in 39% of the cases. The use of early intensification was reported in 8 studies including 194 patients. The CR rate was 51.5%. Overall, the probability of achieving the CR was 2-3 times higher in LD than in ED (extensive disease). Relapses occurred at the site of the primary in more than half of the cases, showing that the course of the disease was not modified by the use of high-dose chemotherapy. Toxic deaths occurred in 7% of the treated patients, without difference in the two treatment methods. Though the schedules were too variable to draw firm conclusions, the ICE (ifosfamide, carboplatin, etoposide) and the CBP (cyclophosphamide, cisplatin, carmustine) regimens apparently provided better results, with a 2-year survival rate of 30-50% in the LD subset. An european multicenter randomized trial is ongoing. At the present time high-dose chemotherapy is still to be considered experimental treatment, since major problems such as the selection of the patients, doses and timing of chemotherapy and radiotherapy remain unsolved.
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PMID:High-dose chemotherapy in small-cell lung cancer. 1255 40