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)

Twenty-three patients with small cell lung cancer were treated with combination chemotherapy consisting of Cisplatin at 100 mg/m2 given by 2 hours intravenous infusion on day 1 and oral etoposide 25 mg/caplet given twice a day for 21 days repeated every 28 days for 6 cycles. Of 23 cases, four cases were not evaluable due to early death (three of them died from febrile neutropenia). Median age of the patients was 59 years (range = 45-76 years). Five cases were female and eighteen cases were male. Median Karnofsky performance status was 70 per cent (range = 50-90%). Five cases were extensive disease and eighteen cases were limited disease. Of 5 extensive disease cases, 1 complete response (20%) and 3 partial responses (60%) were achieved. Of 14 limited disease patients, 1 complete response (7.1%) and 11 partial responses (78.6%) were achieved. Hematologic toxicities were severe causing three patients to die because of febrile neutropenia, nine cases (10.7%) had grade 3 and 4 neutropenia. Grade 3 and 4 anemia and thrombocytopenia were seen in 28.6 per cent and 8.3 per cent respectively. Median survival time of all cases was 7 months. Thus, the combination of intravenous cisplatin and prolonged administration of oral etoposide could be administered to small cell lung cancer patients with high response rate, however, because of its severe toxicities, special caution should be considered and the optimal duration of oral etoposide should be evaluated.
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PMID:Preliminary study of efficacy of intravenous cisplatin plus oral etoposide in small cell lung cancer. 947 Mar 20

We investigated the reconstitutive potential of haematopoietic progenitor cells collected in autologous whole blood during multicycle dose-intensified chemotherapy. Forty patients with metastatic solid tumours were treated with up to six cycles of cisplatin and escalating doses of ifosfamide every 14 days. Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide over 24 h and mesna over 36 h. The first cohort of patients received granulocyte colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was reached in cohort 1, the study continued with a second cohort of patients, in whom, in addition to G-CSF on days 4-14, 500 ml of G-CSF and chemotherapy-'primed' whole blood was collected on day 15, i.e. on day 1 of treatment cycles two to six, before cisplatin administration. This volume of blood was kept unprocessed at 4 degrees C and reinfused 20-24 h after the completion of ifosfamide. In cohort 1, dose-limiting toxicity (DLT) was reached at ifosfamide 6.0 g m(-2) with two out of six of the patients developing neutropenic fever. Although in cohort 2 no neutropenic fever was encountered, neither the frequency nor the duration of grade 4 neutropenia and thrombocytopenia were reduced. Cumulative asthenia resulted in DLT at 7.0 g m(-2). The median number of CD34+ cells in 500 ml of whole blood after the first cycle (i.e. at start of cycle 2) was 1.15 x 10(6) kg(-1). This number was significantly greater after the second cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually decreased after cycles three to six. After storing whole blood, the number of CD34+ cells had not decreased (median + 10%). We conclude that the method of combined bone marrow support by G-CSF and haematopoietic progenitor cells in autologous whole blood collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does not result in clinically measurable reduced bone marrow toxicity compared with what can be expected by the use of G-CSF alone.
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PMID:A phase I/II study of multicyclic dose-intensive chemotherapy supported with G-CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two consecutive cohorts of patients. 964 59

Twenty-three patients with brain metastases from non-small cell lung cancer (NSCLC) (median age 62 years, Karnofsky PS 50-100) were treated with cisplatin (100 mg/m2, day 1) and teniposide (80 mg/m2, days 1, 3 and 5) every 3 weeks. Response was evaluated by contrast-enhanced brain CT every two to three cycles of treatment. The objective response rate of brain metastases was 35% (8/23); three patients achieved complete response (CR) and five partial response (PR). The median response duration was 24 weeks for CR patients and 32 weeks for PR patients. The median survival was 21 weeks overall and 45 weeks for responding patients. Grade 3/4 leukocytopenia and thrombocytopenia were seen in 28 and 9%, respectively. Two patients died from infections while in neutropenia. Cisplatin and teniposide seems an active regimen against brain metastases in NSCLC. These data may indicate the need for reconsideration of the role of chemotherapy for brain metastases of NSCLC.
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PMID:Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer. 971 27

Single-agent therapy with paclitaxel is effective against both squamous cell carcinoma and adenocarcinoma of the oesophagus. However, only limited data are available on the combination of paclitaxel with other cytotoxic drugs in this entity. Patients with unresectable stage III, recurrent or metastatic tumours were treated in a multicentre setting with paclitaxel 90 mg m(-2) given over 3 h intravenously, followed by cisplatin 50 mg m(-2). The courses were repeated every 14 days. Twenty patients with squamous cell carcinoma or adenocarcinoma of the oesophagus were evaluable for response. The overall remission rate was 40% (8/20), including 15% (3/20) clinically complete responses. Clinical benefit response, defined as relief of dysphagia and/or significant gain in weight, was achieved in 70% of the patients. Neutropenia of CTC grade 3 occurred only in 10% of the patients; no grade 4 neutropenia and no severe thrombocytopenia was encountered. CTC grade 4 neurotoxicity was seen in 5% of patients. Cisplatin/paclitaxel administered every 14 days, was effective in patients with poor prognosis oesophageal cancer and toxicity was acceptable.
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PMID:Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. 971 36

Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, patients were initially treated with weekly brequinar, in combination with an every-three-week administration of cisplatin. Due to toxicity, the schedule was modified to a 28-day cycle with brequinar given on days 1, 8, 15, and cisplatin on day 1. A total of 24 patients (16 male, 8 female; median age 57; median performance status 1) received 69 courses of therapy. Six dose levels were explored, with cisplatin/ brequinar doses, respectively, of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2. The serum concentration versus time curves for brequinar were biphasic. A comparison of the pharmacokinetic results after the first and third doses of brequinar indicate that the presence of 50, 60, and 75 mg/m2cisplatin did not change the protein binding and the pharmacokinetics of brequinar in any of the three brequinar-dose groups. Total cisplatin plasma pharmacokinetic followed a triphasic-shape curve and unbound cisplatin decayed at a very rapid rate. Since pharmacokinetic parameters for total cisplatin in this study were similar to those reported in the literature, the presence of brequinar is unlikely to alter the pharmacokinetics of cisplatin. Main dose-limiting toxicities included myelosuppression (including neutropenia and thrombocytopenia) and mucositis. Cisplatin/brequinar doses of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2, were associated with dose limiting toxicity in 0/3, 1/3, 1/3, 1/3, 2/4, 2/5, and 4/6 patients, respectively. This study shows that co-administration of brequinar and cisplatin does not affect the pharmacokinetic properties of either drug and that the MTDs of cisplatin/brequinar combinations are 60/860 mg/m2 or 75/650 mg/m2. From this study, we conclude that full dose of 75 mg/m2 cisplatin (day 1) can be administered with 650 mg/m2 brequinar (days 1, 8 and 15) without significant modifications of individual drug pharmacokinetic parameters.
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PMID:Pharmacokinetic and phase I studies of brequinar (DUP 785; NSC 368390) in combination with cisplatin in patients with advanced malignancies. 974 May 40

Forty-three patients with ovarian cancer were entered on this trial and treated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and intraperitoneal (ip) cisplatin (DDP), every 21 days for eight cycles. Following iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are evaluable for overall and progression-free survival with a median follow-up of 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (range 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were stage III (optimally debulked), 14 patients were stage III (suboptimally debulked), and 7 patients were stage IV. Two patients had received prior alkylator therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally debulked stage III patients, there were 7 complete responses, 3 partial responses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 suboptimally debulked stage III patients there were 4 complete responses, 4 partial responses, 3 with stable disease, 2 progressions on treatment, and 1 inevaluable patient. Five-year progression-free and overall survivals for stage III optimally debulked patients are 21 and 64%, respectively. At 10 years, progression-free and overall survivals for this group are 21 and 29%, respectively. Toxicity included neutropenia (complicated by sepsis in 2 patients), infrequent thrombocytopenia, and mild anemia. Three patients developed transient serum creatinine elevations >2.0 mg/dl; however, decreased creatinine clearance was noted in 93/258 (36%) of evaluable courses which required a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free and overall survivals that compare favorably with those of other published studies of intravenous or intraperitoneal chemotherapy. This report is unusual in terms of the prolonged follow-up for all patients enrolled. These long-term results lend further support to recently published trials documenting the efficacy of intraperitoneal chemotherapy for patients with this disease.
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PMID:Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up. 1060 Mar

The medical treatment of squamous cell cervical carcinoma is receiving increasing attention. Cisplatin and ifosfamide are known effective drugs. Paclitaxel has been tested with interesting results in cervical cancer. We evaluated the toxic effects and the antitumor activity of a multiagent regimen that included paclitaxel, ifosfamide, and cisplatin (TIP) in two different settings: bulky and locally advanced cervical cancer and recurrent-persistent disease. Treatment consisted of paclitaxel 175 mg/m2 given over 3 hours on day 1, cisplatin 50 mg/m2 (75 mg/m2 in 24 patients), ifosfamide 5 g/m2 and mesna 5 g/m2 given on day 2, and mesna 3 g/m2 given on day 3. In the neoadjuvant setting, the course was repeated every 3 weeks for three courses. Unless there was progression of disease or reason to avoid surgery, all patients were scheduled for radical hysterectomy and pelvic lymphadenectomy. Thirty-eight patients with locally advanced cervical cancer were studied: 11 women achieved a clinical complete response, 21 had a partial response, five had stable disease, and one had disease progression. Among the 34 patients who underwent surgery, six had a pathologically documented complete response, seven had an optimal partial response (only microscopic residual disease), 19 had a suboptimal partial response, and two stable diseases. Grade 3-4 neutropenia was recorded in 71% of patients, grade 3-4 thrombocytopenia in 10.5%, and grade 2 peripheral neuropathy in 2.6%. With a median follow-up period of 22 months for the patients who remain alive, 28 women are alive without recurrence and five are alive with persistent/recurrent disease. Five patients have died of disease. In the salvage setting, 45 women with persistent-recurrent disease after primary treatment were treated; 31 of these women had received prior radiation. In the salvage setting we observed 15 clinical complete responses, 15 partial responses, nine stable diseases, and six disease progressions. The objective response rate was 66.6%. Ten complete responders underwent subsequent surgery and seven had pathologic complete response (two in radiated areas). The response rate was 52% in radiated areas and 75% in nonradiated areas. The median survival time is 6 months for the nonresponders, 9+ month for the partial responders, and 13+ months for the complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3-4 myelotoxicity. One woman had life-threatening toxicity. This regimen yields a high response rate with acceptable toxicity and should be prospectively compared with other regimens. The high rate of pathologic complete and optimal responses might impact positively on survival, but only a longer follow-up period will allow objective assessment of this impact. The specific roles of paclitaxel and ifosfamide in this regimen remain to be fully understood.
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PMID:Chemotherapy with paclitaxel, ifosfamide, and cisplatin for the treatment of squamous cell cervical cancer: the experience of Monza. 1069 40

Cisplatin (CDDP), epirubicin (EPI) and docetaxel have single agent activity against urothelial transitional cell carcinoma (TCC). We evaluated the efficacy and toxicity of this combination in locally advanced or metastatic urothelial TCC. Patients with urothelial TCC who had no prior chemotherapy (prior adjuvant chemotherapy > 6 months allowed) were eligible for entry the study. Eligibility criteria were performance status 0-3, granulocyte count (AGC) > or = 1.5 (10(9)/l), platelet count > or = 100 (10(9)/l), clearance creatine > or = 60 ml/min and total bilirubin level < or = 1.5 mg/dl. Treatment consisted of EPI 40 mg/m2 intravenous push, docetaxel 75 mg/m2 in 1 h infusion with premedication and CDDP 75 mg/m2 with pre- and posthydration. Treatment was repeated every 21 days. Antiemetics with dexamethasone and 5-HT3 antagonists were used routinely. Prophylactic haematopoietic growth factors were not used. Patients were evaluated for toxicity weekly and assessed for response every two cycles of treatment. 32 patients were entered into the study and 30 patients (7 with locally advanced and 23 with metastatic disease) were assessable for response. There were 9 (30.0%) complete responses (2, 28.6% in locally advanced and 7, 30.4% in metastatic disease) and 11 (36.7%) partial responses (3, 42.9% in locally advanced and 8, 34.8% in metastatic disease) with an overall response rate (RR) of 66.7% (71.5% in locally advanced, 65.2% in metastatic disease). Overall median survival was 14.5 months (15 months for locally advanced, 12.5 months for metastatic disease). The median duration of response in patients with metastatic disease was 8.5 months. 16 (53.3%) patients required one dose reduction and 5 (16.7%) patients required two dose reductions for a nadir AGC < or = 500/mm3. Four episodes of febrile neutropenia and sepsis occurred. No patient had a dose reduction or treatment delay for any other grade 3/4 toxicity. There were no treatment delays due to myelotoxicity. Alopecia was universal. Non-haematological toxicity including mucositis, fluid retention, allergy, cutaneous toxicity, diarrhoea and neurotoxicity were mild and infrequent. The combination of EPI, docetaxel and CDDP is an active regimen for urothelial TCC. The response rate and toxicity were comparable with the M-VAC (methotrexate, vinblastine, doxorubicin, cisplastin) regimen. Phase III trials comparing this regimen with M-VAC are warranted.
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PMID:Chemotherapy with cisplatin, epirubicin and docetaxel in transitional cell urothelial cancer. Phase II trial. 1074 Dec 98

The objective of this phase II prospective study was to determine the efficacy and the toxicity of a new schedule of neoadjuvant chemotherapy in locally advanced squamous cell carcinomas of the head and neck (SCCHN). Thirty-three patients were included in this study (13 stage III and 20 stage IV). Cisplatin (CDDP: 35 mg/m2), 5-fluorouracil (FU: 2 g/m2) and folinic acid (FA: 500 mg/m2) were administered by continuous i.v. infusion for 24 h, once every 7 days. Six cycles of neoadjuvant chemotherapy were planned before definitive locoregional treatment. A total of 195 cycles were analysed for toxicity: mucositis was observed in 11/195 cycles; 12/195 showed diarrhea and vomiting occurred in 10/195. The myelosuppression was low (neutropenia: 4/195, thrombopenia: 3/195). One treatment-related death was observed after grade IV neutropenia at the fourth cycle. Thirty-two patients were evaluated for response. The objective response rate was 87%, with 50% complete response (CR) and 37% partial response. Failure rate was 13% (stable disease). There was no progressive disease. Survival and DFS duration were significantly higher in cases of CR or in laryngeal localization. The average peak plasma levels for the 6 courses of CDDP, 5-FU, dl-FA and mTHF were 4.9+/-0.76 microM, 4.1+/-0.54 microM, 29.1+/-2.4 microM and 4.8+/-0.31 microM respectively. Therefore, the administration of the 3 drugs by a 24 h continuous i.v. infusion reached an efficient level for drug modulation. This new weekly schedule is as active as other standard therapy in the disease but significantly less toxic as neoadjuvant chemotherapy in advanced untreated SCCHN. With the low toxicities observed with this schedule, additional treatment (surgery and/or radiotherapy) is warranted to evaluate the impact on overall survival of SCCHN.
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PMID:Phase II trial of cisplatin, 5-fluorouracil and folinic acid using a weekly 24-h infusion schedule for locally advanced head and neck cancer: a pharmacokinetic and clinical survey. 1093 96

In our previous phase I/II studies, both the cisplatin (Platinol), gemcitabine (Gemzar), and vinorelbine (Navelbine) (PGV), and cisplatin, gemcitabine, and paclitaxel (Taxol) (PGT) regimens produced a median survival of approximately 1 year in patients with advanced non-small-cell lung cancer (NSCLC). The present phase III study compared the median survival of patients treated with these triple-drug regimens to that of patients receiving cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG). Accrual for the trial began in 1997 and by December 1998, a total of 240 patients (stage IIIB, 98; stage IV, 142) had been enrolled. An interim survival analysis was performed in April 1999. Overall, 151 patients had died. The median survival rates of patients in the PGV, PG, and PV arms were 51, 42, and 35 weeks, respectively. At the time of this analysis, the median survival of patients in the PGT arm could not be assessed; however, the 1-year projected survival rate was 58%. At multivariate Cox analysis, the estimated risk of death for patients receiving PGV compared with those receiving PV was 0.35 (95% CI, 0.16-0.77, P = .0058). Overall response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm, and 58% in the PGT arm. Severe neutropenia and vomiting were significantly more frequent in patients who received PV than in those who received PGV. The PV regimen produced a significantly shorter survival compared with the PGV combination. Since this difference in survival complied with one of the early stopping rules, accrual in the PV arm was discontinued. Enrollment in the PGV, PG, and PGT arms is ongoing.
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PMID:Interim analysis of a phase III trial. Triple- vs double-agent chemotherapy for advanced non-small-cell lung cancer. Southern Italy Cooperative Oncology Group. 1096 Sep 44


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