Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Etoposide phosphate, a water soluble prodrug of etoposide, has several potential advantages including easier and more rapid administration, avoidance of large fluid loads, and elimination of hypersensitivity reactions and other problems related to the solubilizer. This randomized Phase II study was done to evaluate the efficacy and toxicity of etoposide phosphate and etoposide, when used in combination with cisplatin in the treatment of patients with small cell lung cancer. Previously untreated small cell lung cancer patients were randomized to receive cisplatin in combination with molar equivalent does of either etoposide or etoposide phosphate. The patients were evaluated with respect to response rate, time to progression, survival, and toxicity. Response rates with etoposide phosphate and etoposide were 61% (95% confidence interval 55-67%) and 58% (95% confidence interval 52-64%), respectively (P = 0.85). Median time to progression was 6.9 months for patients who received etoposide phosphate and 7.0 months for those with etoposide (P = 0.50). For extensive stage disease patients, median survival with etoposide phosphate was 9.5 months versus 10 months for etoposide (P = 0.93). The corresponding median survivals for patients with limited stage disease were > 16 months and 17 months, respectively (P = 0.62). Myelosuppression was the most common toxicity; Grade 3 and 4 leukopenia occurred in 63% of patients receiving etoposide phosphate compared with 77% receiving etoposide (P = 0.16). The combination of etoposide phosphate and cisplatin is effective in the treatment of small cell lung cancer, and can be administered with acceptable toxicity. This study was not designed to be a formal Phase III comparative trial, but the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar equivalent etoposide doses. Etoposide phosphate is preferable to etoposide because it is easier to use.
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PMID:Etoposide phosphate or etoposide with cisplatin in the treatment of small cell lung cancer: randomized phase II trial. 755 61

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

Epirubicin is the 4' epimer of the anthracycline antibiotic doxorubicin, and has been used alone or in combination with other cytotoxic agents in the treatment of a variety of malignancies. Comparative and noncomparative clinical trials have demonstrated that regimens containing conventional doses of epirubicin achieved equivalent objective response rates and overall median survival as similar doxorubicin-containing regimens in the treatment of advanced and early breast cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), non-Hodgkin's lymphoma, ovarian cancer, gastric cancer and nonresectable primary hepatocellular carcinoma. Recently, dose-intensive regimens of epirubicin have achieved high response rates in a number of malignancies including early and advanced breast cancer and lung cancer. The major acute dose-limiting toxicity of anthracyclines is myelosuppression. In vitro and clinical studies have shown that, at equimolar doses, epirubicin is less myelotoxic than doxorubicin. The lower haematological toxicity of epirubicin, as well as the recent introduction of supportive measures such as colony-stimulating factors, has allowed dose-intensification of epirubicin-containing regimens, which is particularly significant because of the definite dose-response relationship of anthracyclines. Cardiotoxicity, which is manifested clinically as irreversible congestive heart failure and/or cardiomyopathy, is the most important chronic cumulative dose-limiting toxicity of anthracyclines. Epirubicin has a lower propensity to produce cardiotoxic effects than doxorubicin, and its recommended maximum cumulative dose is almost double that of doxorubicin, thus allowing for more treatment cycles and/or higher doses of epirubicin. In summary, dose-intensive epirubicin-containing regimens, which are feasible due to its lower myelosuppression and cardiotoxicity, have produced high response rates in early breast cancer, a potentially curable malignancy, as well as advanced breast, and lung cancers. Furthermore, there is evidence to suggest that improved response rates can improve quality of life in some clinical settings, but whether this leads to prolonged survival has not yet been determined. Recently implemented supportive measures such as colony-stimulating factors, prophylactic antimicrobials and peripheral blood stem cell support may help achieve other potential advantages of dose-intensive epirubicin-containing regimens such as reductions in morbidity and length of hospital admissions.
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PMID:Epirubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cancer chemotherapy. 768 69

The combination of carboplatin and etoposide is an active and well-tolerated regimen in the treatment of small cell lung cancer (SCLC). The aim of the study was to confirm whether the efficacy could be maintained if etoposide was administered orally. 106 consecutive, unselected, and untreated patients with SCLC (limited disease (LD) 44; extensive disease (ED) 62) were treated with a combination of carboplatin 300 mg/m2 intravenously (i.v.) day 1 and etoposide 240 mg/m2 orally days 1-3 every 4 weeks for six courses or until progression. If oral treatment was inconvenient, i.v. etoposide (120 mg/m2 days 1-3) was allowed. Thoracic irradiation (45 Gy in 22 fractions, split course) was given after three courses of chemotherapy to 29 patients with LD. Objective response (complete and partial) was seen in 89% (confidence interval (CI) 75-97) of patients with LD and in 53% (CI 40-66) with ED. Complete response was seen in 41% (CI 26-57) of patients with LD and in 8% (CI 2-18) with ED. Median time to progression for responders was 11 months and 6 months for patients with LD and ED, respectively. Corresponding median survival was 15 months (range 1-45 months) and 8.5 months (0-26 months). Myelosuppression comprised the main toxicity. Leucopenia (WHO III-IV) was observed in 20% and thrombocytopenia (WHO III-IV) in 16% of the cases. One patient died of sepsis during leucopenia. Oral treatment was convenient for most patients and therapy well tolerated. However, 9 patients (20%; CI 9-36%) with LD and 26 patients (42%; CI 29-56%) with ED received at least part of the etoposide treatment i.v.. The present study shows that the combination of carboplatin and oral etoposide is active and well tolerated, and may be used on an outpatient basis in patients with small cell lung cancer.
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PMID:Is carboplatin and oral etoposide an effective and feasible regimen in patients with small cell lung cancer? 769 81

From March 1987 to February 1991, 136 patients with untreated small cell lung cancer (64 patients with limited disease and 72 with extensive disease), were treated as part of a prospective multi-center study, with a combination of cyclophosphamide 1000 mg/m2 i.v. on day 1, epirubicin 70 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1, 3 and 5. Courses were repeated every 3 weeks. One-hundred thirty-four patients were evaluable. There were 42 (31%) complete responses and 66 (49%) partial responses for an overall response rate of 80% (95% confidence interval 71-87%). A complete response was seen in 24 patients (38%) with limited disease and in 18 patients (26%) with extensive disease, while a partial response was observed for 31 (48%) and in 35 (50%) patients, respectively. The median duration of response for all patients was 8.9 months (range, 1-60+ months). The median duration of survival for the entire group was 11.4 months (12.5 months for limited disease and 9.8 months for extensive disease). The 2-year survival rate for the whole group was 13%. The main side-effects were myelosuppression, alopecia, nausea and vomiting. Grade 4 toxicity was seen in 8.5% of patients. In conclusion, the studied regimen was found to be active and well tolerated and may be considered as an alternative to standard chemotherapy combinations in SCLC.
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PMID:Combination chemotherapy with cyclophosphamide, epirubicin and etoposide in small cell lung cancer. 781 5

In this phase III, double-random study, we compared CAV-E to CAV-T combination as induction treatment (1st randomization) for SCLC. Subsequently, patients achieving a complete response (CR) were randomized again (2nd randomization) to receive maintenance treatment with alpha-IFN or no treatment. From June 1990 to June 1992, 75 untreated patients were enrolled in this trial. After stratification according to limited disease (LD) or extensive disease (ED), patients were randomized to receive the following treatment: cyclophosphamide 1000 mg/m2, adriamycin 50 mg/m2, vincristine 2 mg, day 1 i.v., plus etoposide (E) 100 mg/m2 (CAV-E: arm-A) or teniposide (T) 60 mg/m2 on day 2, 3, 4 i.v., every 3 weeks (CAV-T: arm-B). LD patients after 3 cycles of treatment received chest radiotherapy and 2 further cycles, whereas ED patients received 5 consecutive cycles. Patients who achieved a CR entered the 2nd randomization receiving a-IFN (3 x 10(6) I.U., i.m. daily x 9 months) or no treatment. A second-line treatment with carboplatin 300 mg/m2 plus E (if T was initially used) or T (if E was initially used) was also scheduled for patients achieving less than CR to induction treatment. Preliminary results are as follows: 75 patients were randomized, 72 were eligible for survival (arm-A = 37 and arm-B = 35) and 60 were fully evaluable for response (arm-A = 34 and arm-B = 26). In patients with LD the overall response rate was 79% (CR 21%) in arm-A vs 92% (CR 50%) in arm-B. In patients with ED, the overall response rate was 80% (CR 33%) in arm-A vs 84% (CR 7%) in arm-B. At a mean observation time of about 1 year (range 1-25 months), median survival of LD patients was 15 months in arm-A and 13 months in arm-B (Chi-square = 1.55; p > 0.05); in ED patients survival was 10.8 months and 8 months respectively (Chi-square = 2.88; p > 0.05). Cumulative survival probability was identical (12 months) in all patients of both arms. Toxicity was mainly haematologic and gastrointestinal: WHO grade 3-4 myelosuppression and vomiting were observed in 20% and 11% respectively, of cycles delivered in arm-A, compared to 19% and 8%, respectively, of cycles in arm-B. Two septic deaths occurred with CAV-T, while 1 patient discontinued treatment due to persistent myelosuppression with CAV-E. After the first and second-line treatment 20 patients showed a CR.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Small cell lung cancer (SCLC): a randomized trial of cyclophosphamide, adriamycin, vincristine plus etoposide (CAV-E) or teniposide (CAV-T) as induction treatment, followed in complete responders by alpha-interferon or no treatment, as maintenance therapy. 784 May 27

In a randomized Eastern Cooperative Oncology Group study, single-agent ifosfamide used to treat extensive-disease small cell lung cancer patients produced a 49% response rate compared with 56% for patients receiving standard combination chemotherapy (cyclophosphamide/doxorubicin/vincristine). When the drug was combined with carboplatin and etoposide to treat extensive-disease small cell lung cancer patients, overall response rate was 83%, median survival time was 9 months, and 2-year survival rate was 14%. The major toxicity was myelosuppression. These results confirm those of other investigators who have shown the effectiveness of the ifosfamide/carboplatin/etoposide regimen in treating patients with small cell lung cancer.
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PMID:The place of ifosfamide in chemotherapy of small cell lung cancer: the Eastern Cooperative Oncology Group experience and a selected literature update. 784 38

Significant advances have been made in the treatment of small cell lung cancer (SCLC) during the past two decades. Major and indisputable improvement has been achieved in patients with limited disease. However, progress in extensive SCLC has been more elusive. Despite thousands of patients entered into numerous phase II and phase III studies, it is still debatable whether any particular regimen is superior to older combination chemotherapy regimens first studied 20 years ago. From May 1989 through January 1993, 171 patients with extensive SCLC were entered into a Hoosier Oncology Group phase III study comparing etoposide/cisplatin (VP) with etoposide/ifosfamide/cisplatin (VIP). There were 166 patients fully evaluable for response and survival. As expected, hematologic toxicity was more severe in the patients in the VIP arm, but both arms had a 6% to 7% treatment-related mortality rate. The response rate were similar (70% v 66%, with 18% and 21% complete remissions). However, there was improved survival in the VIP arm (P = .03). This was most pronounced at the tail of the survival curves, with 2- and 3-year survival rates of 12% and 5% for VIP compared with 5% and 0% for VP. A different form of VIP chemotherapy for patients with refractory SCLC with no prior ifosfamide also was evaluated. From February 1990 to August 1993, 46 patients with previously treated SCLC were treated with daily oral etoposide/ifosfamide/cisplatin. Thirty-one of 41 evaluable patients had prior cisplatin plus intravenous etoposide. Myelosuppression was significant, with six treatment-related deaths. Twenty-two of 41 patients (54%) had an objective response, including six (15%) complete remissions. The median length of survival was 29 weeks (range, 1 to 76 weeks). Despite the toxicity, these results are competitive with many first-line chemotherapy programs. This is a reasonable, aggressive regimen for selected patients with refractory SCLC.
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PMID:Hoosier Oncology Group studies in extensive and recurrent small cell lung cancer. 784 39

The aim of this study was to assess the efficacy and toxicity of intensive chemotherapy, administered without dose reduction, with cranial and thoracic radiotherapy given when possible as a single fraction in small cell lung cancer. 87 patients were eligible on the basis of good performance status, normal or near normal biochemistry and clinical staging, 73 limited and 14 extensive stage, computed tomography scanning was not mandatory. Six cycles of carboplatin, ifosfamide and etoposide with vincristine on day 15 at 4 weekly intervals were planned. Dosages were not reduced in response to myelosuppression. Prophylactic cranial irradiation (PCI) as a single fraction after the first cycle and thoracic irradiation (when possible as a single fraction) following the third cycle were delivered. Seventy-two per cent of patients completed the protocol. Complete response rate was 55% and 26% of patients had a partial response. The median nadirs of neutropenia were 0.5 x 10(9)/l and thrombocytopenia 14 x 10(9)/l, with 6% probable treatment-related deaths. Performance status and dyspnoea improved markedly to normal or near normal levels following the second course. Brain metastases occurred in 13% of patients. The median survival was 16.2 months with a 2-year survival of 31% (95% confidence interval, 24-41%) for a minimum follow-up of 26 months. These results compare favourably with other combined modality studies, using multiple radiotherapy fractions with cisplatin-based combinations and dosage reduction for patients staged in more anatomical detail. The toxicity spectrum and efficacy data could lead to the use of this chemotherapy regimen with haematopoietic growth factors and, in the future, peripheral blood progenitor cell rescue.
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PMID:Therapy for small cell lung cancer using carboplatin, ifosfamide, etoposide (without dose reduction), mid-cycle vincristine with thoracic and cranial irradiation. 785 8

Taxol, a diterpene alkaloid isolated from the bark of Taxus brevifolia, has a unique mechanism of action. The drug promotes the formation of microtubule polymers in a cell, by reversibly and specifically binding the beta-subunit of tubulin. Taxol is administered intravenously by a 3-24-hour infusion at 3-week intervals. Myelosuppression, especially neutropenia, appears to be the dose limiting toxicity in solid tumours at 200-250 mg/m2. Furthermore, side effects such as sensory neurotoxicity (with typical numbness, tingling and painful paraesthesiae in the extremities), diarrhoea and alopecia appear frequently. Mucositis appears to be the non-haematological dose limiting side effect at 390 mg/m2 that has been determined in patients with leukaemia. Hypersensitivity reactions, which have been fatal in individual cases, might be schedule dependent. Furthermore, antiallergic prophylaxis must be given, although this precaution might not be considered to be fully protective. Phase I studies performed with combinations of taxol and cisplatin, doxorubicin or cyclophosphamide have indicated the feasibility of these regimens and show promise for future investigations. Addition of granulocyte-colony stimulating factor (G-CSF), aimed at modulating myelosuppressive toxicity, showed in Phase I studies that the taxol dose could be increased to 250 mg/m2, with peripheral neuropathy as the dose limiting toxicity. In Phase II studies, taxol has been shown to be effective, including producing complete tumour remission, in advanced drug refractory ovarian carcinoma (19%-36% response rate), previously treated patients with metastatic breast carcinoma (27%-62% response rate), advanced non-small lung cancer (21%-24% response rate), advanced small cell lung cancer (37% response rate) and advanced head and neck cancer (34% response rate).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical, toxicological and pharmaceutical aspects of the antineoplastic drug taxol: a review. 790 88


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