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)

A series of studies has been carried out to evaluate and document the value of carboplatin in the treatment of patients with small cell lung cancer (SCLC). Encouraging response rates but disappointingly short response durations with both single-agent carboplatin and combination carboplatin/etoposide led to the use of more intensive study regimens. A six-course, dose-intensive study of combination carboplatin/etoposide/ifosfamide in good-prognosis patients resulted in a 97% objective response rate (31 of 32 patients), including 17 (53%) complete responses. However, the toxicity associated with this regimen was expectedly high. In a subsequent phase I dose-escalation study of carboplatin in SCLC, non-small cell lung cancer, and mesothelioma, patients received 800, 1,200, or 1,600 mg/m2 carboplatin given as a 1-hour intravenous infusion. Five of the seven SCLC patients achieved a complete or partial response, but no responses were seen among the other patients. The major toxicity noted was myelosuppression and, while treatment was well tolerated, toxicity was more pronounced at the higher doses. The role of carboplatin as palliative therapy for SCLC patients with advanced disease or poor performance status is currently under investigation with a regimen containing carboplatin/methotrexate/vinblastine. In light of the results of these several studies, it is apparent that carboplatin is an extremely active agent for treatment of SCLC and is not associated with the nephropathy, neuropathy, or severe nausea and vomiting induced by its parent compound, cisplatin. Further study of carboplatin as high-dose therapy, in dose-intensive combination regimens, and as palliative treatment is recommended.
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PMID:Carboplatin in small cell lung cancer: the Royal Marsden Hospital experience. 138 36

Carboplatin is well suited to dose escalation because its major dose-limiting toxicity is myelosuppression when given in 1,200 mg/m2 doses without marrow support. Repeated 800 mg/m2 doses can be given in an investigational setting. With autologous bone marrow rescue the maximum tolerated single-agent dose is approximately 1.8 to 2 g/m2, with dose-limiting toxicities being hepatitis, renal dysfunction, and ototoxicity. Combinations of carboplatin with other agents plus bone marrow rescue are now being investigated in germ cell tumors, ovarian cancer, breast cancer, and small cell lung cancer. High-dose carboplatin plus etoposide combinations are being evaluated with colony-plus stimulating factors in an effort to ameliorate myelosuppression. Future high-dose carboplatin studies could be designed with more predictable toxicity, using an assessment of carboplatin renal clearance. Carboplatin is an important new drug warranting further investigation at escalated doses.
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PMID:Current experience with high-dose carboplatin therapy. 141 26

Etoposide is an important antineoplastic drug. Despite the use of several combination chemotherapy regimens that include etoposide, the best dose and schedule for etoposide remains unknown. The schedule dependency for small cell lung cancer is now known, and it is likely the same for other sensitive neoplasms (ie, lymphoma, germ cell tumors). Recent data suggest that even a more extended schedule of administration (ie, 14 to 21 days) may be more effective than the standard 3- to 5-day schedule. Several studies have assessed plasma levels in reference to dose, schedule, and tumor responsiveness. Preliminary data suggest that high peak levels (ie, > 5 to 10 micrograms/mL) are associated with more severe myelosuppression than lower peak plasma levels (ie, 1 to 3 micrograms/mL). Response rates and survival in small cell lung cancer patients given low daily doses for 14 to 21 days are comparable with results achieved with standard doses given for 3 to 5 days. Preliminary data from several studies suggest that administering low doses for a prolonged schedule is a superior method of etoposide administration. Other studies including randomized comparisons are necessary to confirm these observations.
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PMID:Etoposide: seeking the best dose and schedule. 148 56

Etoposide has been used in the treatment of a wide variety of neoplasms, including small cell lung cancer. Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation, and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include pretreatment leukocyte count, performance status, extent of prior erythrocyte transfusions, and serum albumin level. In the past 5 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies, and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region.
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PMID:New perspectives on the toxicity of etoposide. 149 30

Esorubicin (4'-deoxydoxorubicin or DxDx) is an analog of doxorubicin with preclinical antitumor activity and no significant cardiotoxicity in model systems. Eleven patients with small cell lung cancer who had previously received chemotherapy were given esorubicin (25 mg/m2 intravenously) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-25%). Nine of the 11 patients had grade 2 or greater toxicity, with 55% of the patients experiencing grade 3 or greater toxicity [myelosuppression (4/11), anemia (2/11) or elevated liver enzymes (3/11)]. Nausea, vomiting, alopecia and intravenous site phlebitis were also seen. Three of the 11 patients received 3 or more course of esorubicin without evidence of significant cardiotoxicity. At this dose and schedule, no significant antitumor response were seen in this population of patients. Esorubicin, with this low response rate and significant toxicity, appears to be of limited utility in this disease.
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PMID:Phase II trial of esorubicin (4'deoxydoxorubicin, DxDx) in patients with small cell lung cancer. 165 8

Two hundred twenty-three patients were enrolled on this randomized Phase III trial testing the value of late consolidative involved-field radiation therapy in the treatment of limited-stage small cell lung cancer (SCLC). Patients were treated with induction chemotherapy consisting of alternating cycles of procarbazine, vincristine, lomustine, and cyclophosphamide (POCC) and etoposide, doxorubicin, and methotrexate (VAM) for 6 to 9 months. Responding patients were then randomized at 6 or 9 months to chemotherapy alone or to involved-field radiation therapy. All partial and complete responders received prophylactic cranial irradiation. Of the 180 eligible and evaluable patients, 80 (44%) achieved a complete response and 39 (22%) achieved a partial response (overall rate of response, 66%). Actuarial median survival time was 11.6 months, with 16% of patients surviving 2 years and 11% surviving 5 years. Forty-eight patients were randomized to chemotherapy alone (24 patients) versus chemotherapy plus involved-field radiation therapy (24 patients). There were no significant differences in time to progression or survival between those patients receiving or not receiving involved-field radiation therapy. The thorax was the site of first relapse in 58% of patients randomized to chemotherapy alone versus 29% in patients randomized to chemotherapy plus involved-field radiation therapy (P equals 0.042). The major acute toxicity was reversible myelosuppression, and the major late toxicity was chronic central nervous system dysfunction. The authors conclude that the addition of late consolidative radiation therapy to induction chemotherapy in the treatment of limited-stage SCLC is well tolerated and improves local control, but does not improve time to progression or rates of survival.
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PMID:Late consolidative radiation therapy in the treatment of limited-stage small cell lung cancer. 165 19

The combination of carboplatin and teniposide has been evaluated in a phase II trial including 47 previously untreated patients with extensive small cell lung cancer. Treatment was given at monthly intervals at a dose of 200 mg/m2 of carboplatin intravenously on day 1 and teniposide at a daily dose of 60 mg/m2 intravenously on days 1-5. Treatment response was complete in 4 (8.9%) and partial in 19 (42.2%) of 45 evaluable patients. The overall response rate was 51.1% (95% confidence interval 36%-66%). The median duration of response was 7.1 months (range 2.1-14.8) and the median survival was 6.7 months (0.3-22.2). Myelosuppression was the most prominent side-effect. Leukopenia (WHO grade 3-4) developed in 17 (37.8%) and thrombocytopenia (grade 3-4) in 5 (11.1%) of 45 patients evaluable for toxicity. 2 treatment-related deaths were registered. The present study shows that the combination of carboplatin and teniposide produces an acceptable response rate, but response duration and survival time are short.
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PMID:Treatment of extensive small cell lung cancer with carboplatin and teniposide. 165 51

Sixteen untreated patients with small cell lung cancer were treated with a combination of Etoposide (70 mg/m2 i.v., day 3-5), Cisplatin (40 mg/m2 i.v., days 1 and 8) and THP (20 mg/m2 i.v., days 1 and 8). Cycles were repeated every 4 weeks and 15 patients received more than two cycles. The objective response rate was 80% (12 of 15) in complete cases, 91% (10 of 11) in limited disease and 50% (2 of 4) in extensive disease. CR rate was 33% in complete cases, 46% in limited disease. The median duration of response was 22.6 weeks. The median survival was more than 12 months in complete cases. Toxicity was primarily myelosuppression. Three of 15 patients had leukopenia of grade 4, 3 of 15 of grade 3, and 7 of 15 of grade 2. Nausea and vomiting were well tolerated by metoclopromide and methylprednisolone. The renal toxicity was minimal. There were no chemotherapy-related lethal complications. This schedule of Etoposide, split-dose Cisplatin and THP is effective and safe for patients with small cell lung cancer. However, the advantage of THP is still controversial.
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PMID:[A pilot study of etoposide, split-dose cisplatin and THP in small cell lung cancer]. 166 Jul 1

A total of 14 patients with locally advanced and unresectable head and neck (SCCHN) or non small cell lung cancer were treated with a definitive course of radiation therapy with conventional fractionation and 30 mg/m2 carboplatin (CBDCA) given daily as an i.v. infusion during the 1st, 3rd, 5th and 7th weeks of the combined treatment. The planned tumor dose of at least 7000 cGy was reached in all SCCHN patients except 1 (6600 cGy). The 2 NSCLC patients received 6320 and 5980 cGy, respectively. The planned total CBDCA-dose of 600 mg/m2 was administered in all patients. No treatment delays were required in 10 patients. Interruptions for severe mucositis or myelosuppression occurred in 4 patients (28.6%), but in no case did the delay exceed 1 week. Complete response was obtained in 8 patients (57.1%); 7 of the 12 with SCCHN and 1 of the 2 with NSCLC. The other 6 patients achieved a partial response. Granulocytopenia of WHO grade 3 occurred in 1 patient; apart from vomiting and mucositis, toxicities above grade 2 were not observed.
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PMID:Daily low-dose carboplatin and standard radiotherapy in unresectable head and neck and lung cancers: a pilot study. 166 54

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.
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PMID:Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group. 166 60


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