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)

Methylglyoxal bis-guanylhydrazone (MGBG), a potent inhibitor of polyamine synthesis, has demonstrated single agent activity against a number of tumor types including malignant lymphomas and head and neck, esophageal and non-small cell lung cancers. The growth of small cell lung cancer (SCLC) cell lines can be arrested by polyamine inhibition. Therefore a phase II trial was conducted in twenty-four patients with refractory SCLC. MGBG was administered by intravenous infusion at a dose of 500 mg/m2 per week for four cycles and then every two weeks thereafter. The dose was escalated by 100 mg/m2 every two weeks in the absence of toxicity greater than or equal to grade 2. One patient achieved a partial response of objectively measurable lung disease and supraclavicular adenopathy. Three patients had stable disease. Dose limiting toxicity consisted primarily of mild to moderate nausea, vomiting, stomatitis and/or diarrhea. Myelosuppression was uncommon and rarely dose limiting. We conclude that MGBG in the dose and schedule used does not have significant activity as a single agent in previously treated small cell lung cancer.
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PMID:Phase II trial of methylglyoxal bis-guanylhydrazone (MGBG) in refractory small cell lung cancer. 216 8

A total of 80 patients with limited disease of small cell lung cancer were randomized to receive either vincristine 1 mg/m2 (max. 2 mg), doxorubicin 50 mg/m2 and cyclophosphamide 750 mg/m2 (VAC) i.v. on day 1, or the same drugs and etoposide 80 mg/m2 i.v. daily for 3 days (VACE) every 3 weeks for nine courses. Chest irradiation was given in both regimens after the second course. The response rate was 84% for VAC (41% complete responses) and 75% for VACE (46% complete responses). The median survival time was 10 months with VAC regimen, and 14 months with VACE (difference statistically not significant). The median duration of remission was 8 months with VAC and 14 months with VACE (p = 0.03), and the median survival for complete or partial responders was 12 months and 20 months respectively (p = 0.006). Myelosuppression was significantly greater in the VACE group, and there was one treatment related death in the group receiving VACE. In this study the addition of etoposide to VAC improved the duration of response, but did not lead to longer survival of patients with limited disease of small cell lung cancer.
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PMID:Vincristine, doxorubicin and cyclophosphamide with and without etoposide in limited small cell lung cancer. 216 2

17 previously untreated patients with small cell lung cancer entered a phase II study testing the feasibility of incorporating high dose epirubicin (110 mg/m2, day 1) in combination regimens, including cyclophosphamide (1 g/m2, day 1), and etoposide (120 mg/m2, day 1) (courses 1, 3, 5) or cisplatin (60 mg/m2, day 1) and etoposide (120 mg/m2, days 1-4) (courses 2, 4, 6), every 3 weeks. Complete responders with limited or extensive disease received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. All patients were evaluable for toxicity and response. Myelosuppression and stomatitis were the dose-limiting side-effects. Maximum myelosuppression occurred as granulocytopenia and anemia, but a recovery by day 21 was observed in the majority of courses. Neutropenic fever occurred in 47 of 99 courses. Severe stomatitis was experienced in 25 courses and lasted generally 7-12 days. Acute cardiac toxicity was uncommon and represented by mild to moderate rhythm abnormalities. No change was noted in the mean QRS voltage on electrocardiogram (ECG) and no patient had a decline of greater than or equal to 20% in the cardiac ejection fraction and/or episode of overt heart failure at any stage of treatment. The overall objective response rate was 88%, with six (35%) complete and nine (53%) partial responses. With a median follow-up of 16 months, overall median survival was 13 months (range, 2-18+). This study demonstrates that epirubicin, at the present dose and schedule, is feasible in combination regimens and that cardiotoxicity is not dose-limiting and induced or enhanced by thoracic irradiation and/or cyclophosphamide.
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PMID:Phase II feasibility study of high dose epirubicin-based regimens for untreated patients with small-cell lung cancer. 217 92

Ifosfamide, an analogue of cyclophosphamide, has been proven to be of value in numerous malignancies, including testicular cancer, sarcoma, and lymphoma. Furthermore, ifosfamide is more suitable for combination chemotherapy than its parent compound because it causes less myelosuppression than cyclophosphamide. There have been only a few studies evaluating single-agent ifosfamide in small cell lung cancer (SCLC). In patients who have had little or no prior chemotherapy, ifosfamide appears as active as any single agent. Combination chemotherapy regimens employing cisplatin (or carboplatin) plus etoposide plus ifosfamide are currently under way on both sides of the Atlantic. A Hoosier Oncology Group (HOG) study will evaluate this three-drug regimen v cisplatin plus etoposide, and this protocol will establish or refute the value of ifosfamide as first-line therapy in extensive SCLC.
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PMID:Ifosfamide in small cell lung cancer. 253 44

The effects of hymostimulin on chemotherapy-induced toxicity and long-term survival were studied in 26 evaluable patients with small cell lung cancer. Patients were randomly treated with six cycles of two alternating regimens (cyclophosphamide, 4'-epidoxorubicin, and etoposide; cisplatin and etoposide), with (n = 15) or without (n = 11) thymostimulin (1 mg/Kg i.m., days 7-14 of every cycle). Only complete responders received maintenance treatment, consisting of thymostimulin administered 1 mg/Kg i.m., twice weekly, until tumor relapse. Myelosuppression, fever and documented infectious episodes were significantly less severe in thymostimulin-treated patients, allowing the administration of significantly higher drug doses at shorter intervals between chemotherapy cycles; a significant improvement in complete response rate and survival were also observed. Results suggest that the addition of thymostimulin to standard chemotherapeutic regimens might be of benefit, in view of its favourable effects on toxicity and long-term survival.
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PMID:Effects of thymostimulin on chemotherapy-induced toxicity and long-term survival in small cell lung cancer patients. 253 72

A pilot phase II study of a hybrid chemotherapy for SCLC has been conducted between October 1986 and March 1988. Dose and schedule of the regimen were as follows: CTX, 700 mg/m2, on day 1; ADM 30 mg/m2, on day 1; VCR, 1.4 mg/m2, on day 1 (CAV); and CDDP, 60 mg/m2, on day 8; VP-16, 100 mg/m2, on days 8 and 9 (PVP). Courses were repeated q. 4 weeks up to 6 cycles. Patients with LD received chest irradiation at a dose of 50 Gy when maximal response was achieved. Thirty-six patients were fully evaluated for tumor response and toxicity. All 18 patients with LD responded to the regimen including 11 CRs (61%); there were 7 CRs (39%) and 9 PRs (50%) in patients with ED. Fourteen of the 18 patients with LD have survived for 7 to 22 months, against 12.8 months in ED patients. The major toxicity was myelosuppression, but it was well tolerated. These results indicate that hybrid chemotherapy is highly effective for SCLC, and warrants further clinical trials.
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PMID:[Pilot phase II study of hybrid chemotherapy of CAV-PVP in small cell lung cancer (SCLC)]. 254 49

Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.
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PMID:Phase II studies of mitozolomide in melanoma, lung and ovarian cancer. 254 29

Fifty-five patients with untreated small cell lung cancer were allocated randomly to receive either a standard 2-drug or a 4-drug chemotherapy regimen. The patients were further randomized to receive or not to receive prophylactic cranial irradiation (PCI) 40 Gy/20 fractions/4 weeks. Each patient also received split-course irradiation against the primary tumour (55 Gy/25 fractions/8 weeks), the mediastinum, and the supraclavicular areas. The standard 2-drug regimen consisted of cyclophosphamide 10 mg/kg i.v. days 1-4 and vincristine 1 mg i.v. days 1 + 4; every 4 weeks. The 4-drug regimen comprised cyclophosphamide 10 mg/kg i.v. days 1-3, vincristine 2 mg i.v. day 1 and 1 mg i.v. day 5, methotrexate 30 mg i.v. days 3 and 5, CCNU 80 mg/m2 i.v. day 2; every 7 weeks. The total treatment time for both protocols was 9 to 12 months. Objective response after 2 cycles of chemotherapy was seen in 46% of patients with the 2-drug regimen and in 56% with the 4-drug regimen. Local radiotherapy increased the response rates to 58% and 90% respectively. The median survival time was 12 months with the 2-drug regimen and 14 months with the 4-drug regimen. The 2-year and 3-year survival rates were 11% and 0% in the 2-drug group and 19% and 15% in the 4-drug group respectively. Toxicity was more severe in the 4-drug group with 4 deaths due to myelosuppression. Altogether, 25 patients received PCI. This did not in any subgroup increase median survival significantly but a reduction of relapses in the central nervous system was seen. Median survival was 13 months with versus 10 months without PCI; 2-year survival rates were 15% and 6% respectively. Morbidity due to PCI did not occur. Although no statistically significant survival advantage could be documented, there was obviously a higher rate of complete responses with multidrug therapy, and longer median duration of remission, median survival and maximal survival.
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PMID:Treatment of small cell lung cancer. Two-drug versus four-drug chemotherapy and loco-regional irradiation with or without prophylactic cranial irradiation. 255 55

Forty-two patients with small cell lung cancer were treated with a combination of carboplatin, ifosfamide and etoposide. Vincristine was given on day 14 of each course, the courses being repeated every 28 days for a maximum of six. Thoracic radiotherapy was given 4 weeks after the last course of chemotherapy but no prophylactic cranial radiotherapy was administered. Thirty patients had clinically limited state disease, the remaining patients having contralateral neck lymphadenopathy and/or pleural effusions. Elevated enzyme levels (alkaline phosphatase, LDH, ALT, GGT) were noted in 69% of patients. Twenty-four patients (57%) achieved a complete response (CR) when assessed one month after the end of treatment. A further 21% of patients had a partial response (PR). Median duration of CR was 14 months and of PR 8 months. Cerebral metastases were the sole site of relapse in 13% of the CR patients. Myelosuppression was severe with a median nadir of neutropenia of 0.2 x 10(9) cells 1-1. However, 74% of the patient group received all six courses of chemotherapy and only 16 courses (7%) were delayed because of toxicity. There were three deaths associated with treatment-related neutropenia. The median survival of the total group was 14 months, with an actuarial 2 year survival of 37% and a minimum follow-up of 18 months. [A recent analysis, March 1989, demonstrated a 33%, 2 year actual survival.]
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PMID:Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for 'limited' stage small cell carcinoma of the bronchus. 255 90

The effect of pretreatment with bismuth subnitrate (BSN) for prevention of the renal toxicity of cisplatin (CDDP) was examined in 44 patients with lung cancer (43 non-small cell and one small cell lung cancer). In non-small cell lung cancer cases, the effect of the antitumor activity of chemotherapeutic drugs was observed in 62% of patients pretreated with BSN, and 42% in the group without pretreatment with BSN. No antitumoral activity of chemotherapeutic drugs was suppressed by treatment with BSN. In the group without pretreatment of BSN, serum creatinine and BUN were in proportion to the number of administrations of chemotherapeutic drugs. On the other hand, no renal toxicity was shown in the group with pretreatment by BSN. No protective effect against myelosuppression with pretreatment by BSN was demonstrated, perhaps because of the influence of anti-cancer drugs apart from CDDP.
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PMID:[Prevention of renal toxicity of cisplatin by administration of bismuth subnitrate]. 255 15


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