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)

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.
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PMID:Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer. 169 57

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy. The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60%. In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses. It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%). The administration of antibiotics was required for about 7 days to patients with febrile episodes. Sepsis was experienced in five courses, in which the neutrophils were all zero. All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy.
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PMID:The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor. 172 56

Teniposide is one of the most active agents in small cell lung cancer (SCLC). Because of the experimental evidence of synergistic activity between teniposide and methotrexate and between vincristine and methotrexate, 34 SCLC patients were treated with a combination of teniposide, vincristine, methotrexate and cyclophosphamide. Chest radiotherapy was given to responding patients with limited disease and prophylactic cranial irradiation was given to complete responders only. Most patients had extensive disease and good performance status. The main side-effects were myelosuppression, mucositis and peripheral neuropathy, which were all common and often severe. A response rate of 78% with 22% complete responses was obtained in 32 evaluable patients. Median durations of responses and survival were 252 and 311 days, respectively. Patients with limited disease had a median survival of 556 days while extensive disease patients had a median survival of 240 days. 2 patients with limited disease have been in continuous complete remission for more than 2 years from start of treatment.
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PMID:Pilot study of teniposide in combination chemotherapy for small cell lung cancer. 185 Oct 21

Etoposide underwent conventional Phase I testing in the 1970s. The dose-limiting toxicity in these studies was mild myelosuppression; other toxicities were infrequent. If a greater degree of myelosuppression is accepted, higher than standard doses could be given. This approach takes advantage of the steep dose-response relationship for most chemotherapeutic agents, including etoposide, as shown in early in vitro and clinical studies. Thus, etoposide was considered an ideal agent for further dose-escalation studies, given its wide range of clinical antitumor activity at standard doses, steep dose-response curve, mild bone marrow suppression, and few nonmyeloid side effects. The high-dose etoposide studies that followed used improved and more intensive hematologic supportive care, including, in some trials, autologous marrow transplantation. When etoposide was used as a single agent in these high-dose trials, mucositis, and, to a lesser degree, hepatic dysfunction were dose-limiting. The maximum tolerated dose (MTD) in this setting was 2.4 to 3.0 g/m2. Multi-agent Phase I trials with etoposide and cyclophosphamide, total body irradiation, carmustine, or carboplatin also resulted in dose-limiting mucosal toxicity, with liver and lung problems appearing more often than with high-dose etoposide alone. The toxicity and MTD can be influenced markedly by the schedule of administration. Etoposide as a continuous intravenous infusion can be given at doses of 4.2 g/m2 (with 200 mg/kg cyclophosphamide) with similar toxicity, but without marrow support. The antitumor results in the lymphomas set the stage for treatment of solid tumors, where treatment of patients with "sensitive" relapses had the best outcome. Lymphoma patients had an 80% response rate; overall, long-term (greater than 2 years) disease-free survival was approximately 40%. Germ cell tumors were also responsive, and the same pattern of sensitive relapses and improvement in responding patients was seen (50% to 75% of patients greater than 1 year). In breast cancer and small cell lung cancer (SCLC), high-dose etoposide-containing regimens were used to intensify standard therapy. The results in these settings were not quite as good (breast cancer, 30% disease-free survival at 2 years; SCLC, 10% at 2 years).
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PMID:High-dose etoposide and marrow transplantation. 198 30

An 87-year-old female was admitted with left chest pain and dyspnea in January 1989. The chest X-ray film revealed complete atelectasis of the left lung. Bronchoscopic observation revealed a tumor which was bleeding easily at left main bronchus. Cytological findings of the bronchial aspirates showed small cell lung cancer. Because she was old and had some complications, she was difficult to treat by standard combination chemotherapy. Only etoposide at 150 mg/day was administered orally for 3 days (first course). After the first course the whole lung atelectasis improved; and after the second course (etoposide at 150 mg/day for 4 days) the tumor of the left main bronchus disappeared under endoscopic examination. Malignant cells were not detected in the bronchial aspirates and biopsy specimens. No severe side effect except for alopecia and mild gastrointestinal symptoms such as nausea and vomiting was noted. Myelosuppression was not evident. This case suggested that etoposide administered orally is useful in the treatment of small cell lung cancer especially in elderly patients with complications.
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PMID:[An elderly case of small cell lung cancer showing complete response by oral administration of etoposide]. 215 68

The high activity of carboplatin as a single agent in small cell lung cancer was first identified in 30 previously untreated patients who had a 60% response, which included a 10% complete remission (CR). In this and subsequent studies, carboplatin showed high activity without the nephrotoxicity and neurotoxicity associated with cisplatin. Gastrointestinal side effects and alopecia were also generally mild; the major toxicity was myelosuppression. Two important studies of carboplatin 300 mg/m2 and etoposide (300 to 400 mg/m2) in divided doses have reported objective responses of 85% (21% CR) and 65% (21% CR) in previously untreated patients. However, the median survival in the first study was only 9.5 months in both limited- and extensive-stage patients. In this study, 19% of patients had substantial dose reductions because of myelosuppression. The second study reported a better median survival of 15.3 months for limited-stage patients and 8.3 months for extensive-stage patients. These patients received a maximum of six courses of chemotherapy as opposed to four in the first study, and cranial irradiation in addition to mediastinal irradiation. There also appeared to be fewer dose reductions, ie, 11% for carboplatin. Another study using the combination of carboplatin and etoposide in extensive-stage patients only reported a 56% response rate, including 16% CR and a median survival of 8.1 months. The major toxicity in these three studies was myelosuppression, particularly leukopenia, but only three neutropenia-associated deaths occurred in a total of 180 patients. A recent study has reported the use of similar doses of carboplatin and etoposide in combination with ifosfamide 5 g/m2 (with mesna) and midcourse vincristine. Thoracic radiotherapy was given after six courses of chemotherapy in responding patients, but no cranial irradiation was used. In 42 patients, 30 of whom had limited-stage disease, the response rate was 78%, including a 57% CR rate. The median survival was 14 months, and the 2-year actual survival rate is 33%. These and other studies of carboplatin combinations (which are only preliminary) have described high response rates and possibly improved survival compared with less intensive therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Carboplatin in small cell lung cancer. 215 59

Etoposide is a useful antineoplastic drug, but its optimal dose and schedule of administration remain unknown. In small cell lung cancer (SCLC), an intravenous dose given on a 5-day schedule is clearly superior to the same dose given over 1 day. The standard dose has been in the range of 300 to 500 mg/m2 divided over 3 to 5 days. Whether this schedule dependency (superiority) extends beyond 5 days is unknown. We have investigated patients with several refractory neoplasms who were given oral etoposide over a long-term period (21-day cycles) in a phase 1 trial. The maximum tolerated dose is 50 mg/m2/d for 21 days. The major toxicity is myelosuppression, which usually resolves by days 28 to 35. Responses were seen in several patients. Phase II trials are under way, and it appears that the long-term daily administration of etoposide is more active than the standard schedule. Responses have been seen in refractory germ cell tumors, lymphomas, and SCLC in patients who have progressed on the standard dose and schedule of etoposide. In addition, the drug may be active in soft tissue sarcoma. Preliminary results of combination chemotherapy with cisplatin show good tolerance and activity. The long-term daily administration of etoposide may prove to be a superior schedule and, as such, may be incorporated into combination chemotherapy for several neoplasms.
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PMID:Chronic daily administration of oral etoposide. 215 61

The alkylating agent ifosfamide, an analogue of cyclophosphamide, has undergone extensive testing in the treatment of bronchogenic carcinoma. Available data indicate that ifosfamide as a single agent can effect a 50% objective response rate in small cell lung cancer (SCLC) and a 25% response rate in non-small cell lung cancer (NSCLC). With mesna uroprotection, the primary dose-limiting toxicity is myelosuppression. In combination with other active agents, ifosfamide has yielded high response rates in both SCLC and NSCLC. Results of recent trials indicate that ifosfamide can be used safely in combination chemotherapy. Determination of the precise role of this agent in overall management of bronchogenic carcinoma requires additional study, however.
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PMID:Overview of ifosfamide in small cell and non-small cell lung cancer. 215 87

Based on experimental observations that verapamil and tamoxifen reverse multiple drug resistance, the authors investigated the feasibility of combining both agents with the initial chemotherapy of extensive small cell lung cancer. Overall, in a consecutive series of 58 patients the most important toxicity was myelosuppression, and there was a 24% rate of severe infections. Therapeutic results included 24% complete and 34% partial response rates, median time to disease progression of 32 weeks, and median survival of 46 weeks. In three consecutive cohorts of patients the dose of either tamoxifen or verapamil were escalated by 25% and 33%, respectively. The cohort of patients receiving verapamil 360 mg/day and tamoxifen 100 mg/day (level 2) had slightly more toxicity but also more responses than the other groups. Therefore, the authors recommend that these doses be used in controlled trials to confirm the promising results of their study.
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PMID:Addition of verapamil and tamoxifen to the initial chemotherapy of small cell lung cancer. A phase I/II study. 216 72


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