Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

24 patients with good risk non-seminomatous germ cell tumours (GR-NSGCT) were enrolled in a phase II trial combining carboplatin (C) and etoposide (E). Carboplatin was given at a fixed dose of 450 mg/m2 at d2, and E 120 mg/m2, dl-3, every 4 weeks x 4 cycles (cy). Myelosuppression was the major toxicity with neutropenia grade 4 in 18 cy (19%) and grade 3 in 26 cy (27%). Thrombocytopenia grade 3 and 4 occurred in 7 and 1 cy, respectively. Responses included: 20 complete responses (CR) (83%) with 16 clinical CR and 4 pathological CR; 3 additional patients had complete surgical removal of residual disease (SRRD) with viable tumour (surgical CR); 1 patient progressed during C+E therapy. 5 of the 16 clinical CR relapsed, and all the 3 surgical CR progressed despite post-operative salvage chemotherapy. Adverse events occurred in 9 patients (37.5%; 95% C.I., 19-59%). After a median follow-up of 24 m (range 14 to 38) 4 patients had died [3 progressive disease (PD), 1 suicide while in CR], 3 were alive with PD, and 17 had no evidence of disease. No significant correlation between area under the curve values of carboplatin, overall treatment failure and the platelet nadirs was observed. We conclude that the efficacy of the C+E regimen as given in our protocol is inferior to the standard cisplatin-containing regimens. The low dose-density (D/I) of carboplatin could be responsible for the high failure rate.
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PMID:High failure rate of carboplatin-etoposide combination in good risk non-seminomatous germ cell tumours. 808 Jun 98

Carboplatin, a platinum analog with single-agent activity in previously untreated breast cancer, is characterized by comparatively less renal toxicity and emesis than cisplatin. We combined carboplatin at different dose levels [from 200 to 350 mg/m2 by intravenous (IV) infusion on day 1] with 5-fluorouracil (500 mg/m2 IV on days 1 and 8) and cyclophosphamide (500 mg/m2 IV on day 1), with all three drugs recycled every 28 days, to evaluate anti-tumor activity and toxicity of this novel combination [5-fluorouracil/carboplatin/cyclophosphamide (FCC)] in untreated locally advanced (LABC) or metastatic breast cancer (M+). Of 37 patients treated between March 1990 and August 1991 [LABC 25, M+ 8; World Health Organization (WHO) performance status, 0-1; median number of treatment cycles, 5; median follow-up, 20 months], 33 are evaluable for response and toxicity. The overall complete plus partial remission rate was 57% (LABC 68%, M+ 25%). The median duration of response was 19+ months. The cumulative carboplatin dose ranged from 800 to 2350 mg/m2 (median, 1450 mg/m2). In this series, no correlation was observed between the carboplatin dose level and response rate or toxicity. Leukopenia and thrombocytopenia represented the most frequent toxicities. WHO grades 3 and 4 neutropenia were documented in 34% and 8% of patients, respectively. Thrombocytopenia below 50 x 10(9)/l was observed in 8%. No renal toxicity was observed, and moderate emesis occurred in 67% of patients. These results indicate that FCC is an active and relatively safe combination for the treatment of advanced breast cancer in patients not previously treated with chemotherapy.
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PMID:Carboplatin in combination as first-line therapy in advanced breast cancer. 822 14

The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-small cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECOG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/m2/day, days 1 through 3 and 29 through 31). This was followed by 100 mg/m2 weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks after the completion of combined-modality therapy. All 28 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m2; range, 195 to 586 mg/m2). World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia were observed in 53 and 34% of patients, respectively. There were three febrile neutropenic episodes, but no septic deaths. Five patients (18%) required dose reductions prior to the second chemotherapy cycle, but the dose intensity of carboplatin was maintained (average dose, 390 mg/m2; range, 195 to 586 mg/m2). In all, 82% of patients received full-dose radiotherapy, and 73% received at least five of six planned concurrent weekly carboplatin doses. Carboplatin doses were most frequently delayed for thrombocytopenia and/or leukopenia. Carboplatin did not increase the incidence of radiation-induced esophagitis. Only three patients required interruption of radiotherapy, for esophagitis (two patients) and persistent thrombocytopenia (one patient). The response rate to pre-operative therapy was 64%. In this study, we demonstrated the ability to deliver escalated doses of carboplatin with standard-dose etoposide as induction chemotherapy with reasonable myelotoxicity. The combined-modality therapy was well tolerated, and the addition of weekly carboplatin did not result in increased radiation-related toxicity. This neoadjuvant regimen is active in the treatment of locally advanced NSCLC, and compares favorably to other cisplatin-based regimens.
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PMID:Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer. 822 17

CBDCA has only modest activity against NSCLC, but it is less toxic than cisplatin (CDDP). And CB DCA has a proven synergistic effect with etoposide. On the other hand, etoposide is schedule dependent and when give daily peros has activity against several tumors. So we conducted a trial to evaluate the efficacy of a combination of CBDCA and chronic daily administration of oral etoposide for previously untreated unresectable NSCLC. The treatment schedule consisted of CBDCA 400 mg/m2 on day 1 and chronic daily administration of oral etoposide of 50 mg/day/body for 21 consecutive days every 28 days. Twenty-nine of 36 enrolled patients were eligible. The response rate was 27.6% (95% confidence interval: 11.1-43.9%). The median survival time was 405 days. The primary toxicity was myelosuppression: leukopenia, neutropenia, anemia and thrombocytopenia of Grade 3 or 4 were 14.7%, 29.4%, 26.5%, and 5.9%, respectively. No bleeding episodes or toxic death were observed. Nonhematologic toxicity was slight, and there was no severe gastrointestinal toxicity. This combination was effective against NSCLC with tolerable toxicity and an "easily tolerated outpatient regimen".
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PMID:[Treatment of unresectable non-small cell lung cancer (NSCLC) with carboplatin and chronic daily administration of oral etoposide]. 829 16

Thirty-two patients with locally advanced head and neck cancer have been treated with concurrent weekly carboplatin and conventional radiation therapy (RT) (2 Gy fractions 4-5 days/week to a total dose of 64-70 Gy over 7-8 weeks) in a Phase I/II study. Carboplatin was administered weekly during RT at doses of 75-150 mg/m2/wk as a 1-hour infusion. The maximum tolerated dose of carboplatin was 130 mg/m2/wk, with myelosuppression, predominantly neutropenia, being dose limiting. Other systemic toxicities were insignificant and no overlapping toxicity was evident. Ultimate locoregional control and survival probabilities were disappointing. It is suggested that either further studies using radiation and carboplatin at the dose 130 mg/m2/wk, or variations on dose and scheduling be performed prior to the instigation of Phase III studies.
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PMID:Phase I/II study of concurrent weekly carboplatin and radiation therapy in advanced head and neck cancer. 834 34

Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights ( < 40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m2. Neutropenia was the dose-limiting toxicity in this study.
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PMID:Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993). 868 84

Recombinant human interleukin 3 (rhIL-3) has been suggested to be a useful agent for the treatment of chemotherapy-induced thrombocytopenia. For evaluation of this possibility, rhIL-3 was given subcutaneously for 10 days to patients with small-cell lung cancer (SCLC). Chemotherapy consisted of carboplatin (CBDCA) given at 400 mg/m2 to previously untreated patients or at 350 mg/m2 to previously treated patients on day 1 and etoposide (VP-16) given at 100 mg/m2 on days 1-3 every 4 weeks. If the platelet count nadir was < 75,000/microliters in the control cycle of chemotherapy, patients were randomly assigned for the next cycle to rhIL-3 given at 5 or 10 micrograms/kg per day on days 4-13. A total of 41 patients (32 previously untreated patients and 9 previously treated patients) were enrolled in the study. The platelet count nadir in the cycles including rhIL-3 was significantly higher at both dose levels (P < 0.01) than in the control cycle. The duration of thrombocytopenia (< 75,000/microliters) and the mean time from the 1st day of chemotherapy to thrombocyte recovery (> 100,000/microliters) in the rhIL-3 cycle were significantly shorter than those in the control cycle (P < 0.01). The neutrophil count nadir and the duration of neutropenia (<1,000/microliters) were also significantly improved in the rhIL-3 cycle (P < 0.05). The major side effects were fever (80.5%), headache (24.3%), and fatigue (14.6%). All side effects were tolerable and of less than grade II. There was no difference in the efficacy of the two dose levels, but the 5-micrograms/kg dose appeared to be better tolerated than the 10-micrograms/ kg dose. We conclude that rhIL-3 administration following chemotherapy consisting of CBDCA and VP-16 reduces the incidence and severity of chemotherapy-induced thrombocytopenia and neutropenia with an acceptable adverse-events profile.
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PMID:Phase II study of recombinant human interleukin 3 administration following carboplatin and etoposide chemotherapy in small-cell lung cancer patients. SDZ ILE 964 (IL-3) Study. 876 25

Gemcitabine has shown phase II activity against a range of solid tumor malignancies. This study evaluated a combination of gemcitabine and carboplatin in a phase I trial in 13 chemotherapy-naive patients with non-small cell lung cancer to determine the maximum tolerated dose of carboplatin in combination with gemcitabine. Gemcitabine at a dose of 1,000 mg/m2 was administered on days 1, 8, and 15 of a 28-day cycle and carboplatin was given as a 30. minute infusion immediately before gemcitabine on day 1. Carboplatin dosing was escalated and determined using the Calvert formula, and three patients were treated at the initial predicted dose of area under the curve (AUC) 4 mg/mL/min. Subsequently the carboplatin dose was escalated to a predicted AUC 5.2 mg/mL/min. Pharmacokinetic studies were performed measuring gemcitabine and carboplatin (total platinum) concentrations. Responses were assessed following two cycles of treatment and patients with stable disease or objective responses proceeded to receive a maximum of six cycles. Dose-limiting myelosuppression was identified at a predicted carboplatin AUC 5.2 mg/mL/min, with two patients developing grade 4 neutropenia and two patients grade 4 thrombocytopenia. However, these grade 4 toxicities were not associated with any serious sequelae. In this preliminary study, four partial responses were observed and the median length of survival for all patients was 45 weeks. Pharmacokinetic parameters for gemcitabine were similar to those in patients receiving 1,000 mg/m2 as a single agent, and for carboplatin showed that the delivered dose was slightly below the calculated dose. There was one treatment-related death due to cerebral edema. The combination was well tolerated by the majority of patients, and symptomatic toxicity was similar to single-agent gemcitabine. The combination of gemcitabine and carboplatin is well tolerated in patients with non-small cell lung cancer, with myelosuppression being the dose-limiting toxicity. Symptomatic toxicities were rare and outpatient treatment was easy. In view of the antitumor activity observed, further examination of this combination is warranted. In the first instance, alternate sequencing of the combination with gemcitabine followed by carboplatin is planned in an extended phase I study prior to phase II evaluation.
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PMID:A phase I study of gemcitabine and carboplatin in non-small cell lung cancer. 889 83

In attempt to develop a new chemotherapeutic regimen including carboplatin (CBDCA), epirubicin (EPI), and VP-16 in extensive small cell lung cancer, with a higher dose intensity compared with previous experience of our group, we determined the maximum tolerated dose (MTD) of VP-16 when administered in association with CBDCA (300 mg/ m2, i.v., day 1) and EPI (75 mg/m2, i.v., day 1), recycling chemotherapy every 3 weeks, with the support of granulocyte-colony-stimulating factor (G-CSF). A total of 15 patients received three dose levels of VP-16 (mg/m2, i.v., daily on days 1-3): 100 (three patients), 120 (six), and 140 (six). G-CSF was administered subcutaneously at the dose of 5 micrograms/kg/day on days 6-15 of each chemotherapy course. The MTD was established at 140 mg/m2 and myelotoxicity, grade 4 neutropenia with death for sepsis in one case and grade 3 thrombocytopenia in three cases, was dose limiting. The recommended dose of VP-16 for a phase II study is 140 mg/m2.
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PMID:Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer. 893 78

A multicentre randomised phase III trial in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) was undertaken to compare the therapeutic activity and toxicity of a cisplatin/carboplatin-etoposide-vinorelbine combination with that of a cisplatin-etoposide regimen. Patients with advanced (stage IIIB-IV) NSCLC were randomised, after stratification for stage (IIIB-IV) and performance status (0-1 and 2), to receive either (A) CDDP 40 mg m-2 + VP16 100 mg m-2 on days 1-3 as standard treatment or (B) CBDCA 250 mg m-2 on day 1 + CDDP 30 mg m-2 on days 2 and 3 + VP16 100 mg m-2 on days 1-3 + NVB 30 mg m-2 on day 1. Therapy was recycled on day 29 in both arms. We hypothesised a 15% minimum increment in the response rate with the experimental regimen over the 25% expected activity rate of the standard regimen. A two-stage design was chosen, which permitted the early termination of the trial (after the accrual of 52 patients in each arm) if the difference in response rates between the two regimens was less than 3% at the end of the first stage. A total of 112 patients (arm A = 57, arm B = 55) were enrolled in the study (53 with stage IIIB and 59 with stage IV), of which 105 eligible patients were evaluable for response on an "intention to treat' basis. Seven patients were excluded because they did not fulfil the inclusion criteria. Fifteen responses were observed in arm A (28%, 95% CI = 17-42) and 13 (one complete) in arm B (25%, 95% CI = 13-37). On multivariate logistic analysis, treatment did not affect the response rate, while stage IV and performance status 2 were significantly associated with a lower probability of response. Median survivals were similar in the two arms (31 vs 27 weeks). The experimental regimen was associated with an extremely poor median survival in patients with poor performance status (21 weeks). On Cox analysis, treatment failed to show a significant impact on survival: stage IV (relative risk = 1.6. CI = 1.0-2.6, P = 0.036) was the only prognostic variable significantly associated with a worse survival outcome and, although poor performance status adversely affected survival, this effect did not reach the level of statistical significance (relative risk = 1.6, CI = 0.98-2.5; P = 0.063). There were no significant differences in non-haematological toxicities between the two arms, although three patients in the control arm had to discontinue the treatment because of the persistence of severe nephrotoxicity (two patients) or neurotoxicity (one patient). In contrast, a significant increase in both neutropenia and thrombocytopenia was observed in the experimental arm. Four treatment-related deaths were registered in arm B (two due to neutropenic sepsis, one to myocardial failure and one to acute renal failure) compared with one toxic death (acute renal failure) in arm A. In view of these results, the trial was stopped and the null hypothesis (< 15% increase in response rate with the experimental regimen) has been accepted. Therefore, our combination does not deserve further evaluation as first-line treatment in advanced NSCLC patients. As our data suggest that an aggressive chemotherapy might have a negative impact on survival of patients with poor performance status, trials to evaluate the activity of new regimens should be conducted separately for each subset of patients with different performance status.
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PMID:Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Gruppo Oncologico Campano. 895 97


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