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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The low surgical cure rate in patients with stage III non-small cell lung cancer has prompted an exploration of multimodality treatment strategies. Mature results are presented from a phase II trial of accelerated hyperfractionated radiation therapy, concurrent paclitaxel/cisplatin chemotherapy and surgery for these patients. Between 1994 and 1997, 45 patients with surgically demonstrated stage III non-small cell lung cancer underwent induction treatment with a 96 h continuous cisplatin infusion (20 mg/m(2) per day) and a 24 h infusion of paclitaxel (175 mg/m(2)) given concurrently with accelerated hyperfractionated radiation therapy (1.5 Gy twice daily) to a total dose of 30 Gy. Induction was completed in ten treatment (12 total) days. Surgical resection was scheduled 4 weeks later with a second identical course of chemoradiotherapy given 4-6 weeks post-operatively, to a total radiation dose of 60-63 Gy. Thirty-five patients had stage III(A) disease and ten had stage III(B) disease (eight with N(3) tumors). Induction toxicity included nausea in 89%, dysphagia in 89%, and neutropenia <1000/mm(3) in 84% which required hospitalization for fever in 40%. There were no toxic deaths during induction. About 40 of the 45 patients (89%) were operable and 32 (71%) were resectable for cure. A pathologic response was identified in 22 patients (49%); five patients (11%) had no residual disease. Fourteen patients (31%) were downstaged to mediastinal node negativity. With a median follow-up of 60 months, the Kaplan-Meier projected 5-year overall survival was 29%; locoregional control 79%; and distant metastatic disease control 38%. The projected 5-year survival for the 14 patients downstaged to mediastinal node negativity was 50%. For the 19 patients with residual ipsilateral mediastinal node involvement at surgery it was 32%. This short-course of paclitaxel and cisplatin chemotherapy and concurrent accelerated fractionation radiation is tolerable despite significant myelosuppression. Locoregional control is excellent and survival is better than historical expectations. Patients downstaged to mediastinal node negativity have a prognosis similar to those with de novo stage I(B) and II disease. Distant metastases are the major cause of treatment failure.
Lung Cancer 2002 May
PMID:Accelerated hyperfractionated radiation, concurrent paclitaxel/cisplatin chemotherapy and surgery for stage III non-small cell lung cancer. 1195 51

Although 60% of those diagnosed with non-small-cell lung cancer are 60 years of age or older, the elderly are often undertreated. Furthermore, those older than age 70 are under-represented in clinical research trials. Tremendous bias exists against treating the elderly; therapeutic nihilism and constrained societal/financial resources conspire to maintain the status quo. In limited stage small cell carcinoma of the lung (SCLC), a pivotal meta-analysis by Pignon et al. showed no obvious benefit for chemoradiation over chemotherapy alone in patients older than 70 years of age. However, more recent trials have revealed a clear-cut benefit for fit elderly patients to receive combined modality therapy versus chemotherapy alone, even though outcome generally remains superior for younger patients. For patients with locally advanced non-small-cell lung cancer, conflicting results exist. Individual trials evaluating combined modality therapy have shown no impairment in survival for older patients, but retrospective analyses of the Radiation Therapy Oncology Group database have demonstrated that increased therapeutic intensity does not translate into improved outcome compared with standard, single daily fraction radiation alone. Weighted survival analyses that deduct time spent with progressive disease or significant toxicity have reinforced this notion. In advanced non-small-cell lung cancer, fit elderly patients who receive platinum-based regimens do as well, or nearly as well, as patients younger than age 70, although the incidence of neutropenia and fatigue is often higher. Platinum doses above 75 mg/m2 every 3 weeks to 4 weeks are relatively more toxic in the elderly than are lower doses. Three separate studies from Italy have formally assessed the elderly. One showed superiority for single-agent vinorelbine versus best supportive care regarding survival rates and quality of life. A second showed a marked survival advantage for combination vinorelbine and gemcitabine versus vinorelbine alone. However, a much larger, more credible study demonstrated no benefit for combination vinorelbine and gemcitabine versus the constituent single agents. To date, no elderly-specific trials have addressed the role of taxanes or of platinum-based combination therapy versus non-platinum monotherapy or doublets. Comprehensive evaluation of comorbidities and their influence on outcome have not been conducted, and there are virtually no data for patients older than age 80.
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PMID:Elderly patients with lung cancer: biases and evidence. 1205 91

The purpose of this trial was to evaluate the feasibility of concurrent paclitaxel/cisplatin and conventional thoracic irradiation in locally advanced non-small cell lung cancer (NSCLC). Ambulatory patients with medically inoperable or unresectable stage II-III NSCLC, and performance status 0-2 were eligible. Patients were not excluded from this trial if they had lost more than 5% of their body weight during the preceding 3 months, and/or if they had small ipsilateral pleural effusion. The initial dose of paclitaxel/cisplatin was 110 and 50 mg/m(2), and was escalated through five dose levels. Four cycles of chemotherapy were planned; the first two cycles were given concurrently with radiotherapy (4 weeks apart), followed by two additional cycles (every 3 weeks). Conventional chest radiotherapy to a total dose of 60 Gy (2 Gy per day) was delivered in 6 weeks. Forty-three patients were enrolled of which 38 were evaluable for response. Dose-limiting toxicities were grade 4 neutropenia (43% of patients) and grade 3 esophagitis (26% of patients) during the chemoradiotherapy phase. Grade > or = 2 acute and late pulmonary toxicity occurred in 10 and 68% of the patients, respectively. In most patients, prompt symptomatic and radiologic improvement was observed with early steroid administration. The volume of lung receiving 15-30 Gy was correlated with late pulmonary toxicity. The overall response was 84% with ten complete and 22 partial responses. The median survival was 16.5 months (95% confidence interval, 9.5 to 25) for those patients evaluable for response. After a median follow-up of 70 months, 5 (13%) patients are alive without evidence of disease. The maximum tolerated dose (MTD) of paclitaxel and cisplatin with concurrent radiotherapy is at dose level 3 paclitaxel (135 mg/m(2)) and cisplatin (75 mg/m(2)). Toxicity, although significant, was manageable in the great majority of the patients. The activity observed with this regimen is particularly noteworthy when considering the advanced nature of these patients, and the fact that patients (N=18) with poor risk factors were included in the study.
Lung Cancer 2002 Aug
PMID:Concurrent chemoradiation therapy with cisplatin and paclitaxel for locally advanced non-small cell lung cancer: long-term follow-up of a phase I trial. 1214 Jan 42

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.
Lung Cancer 2002 Sep
PMID:Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. 1223 2

This phase I study was designed to determine the maximum tolerated dose of carboplatin when administered in combination with a fixed dose of vinorelbine and concomitant radiation therapy in patients with advanced non-small cell lung cancer. Chemotherapy was administered on days 1 and 8 of two 21 day cycles. It consisted of vinorelbine at 15 mg/m(2) and carboplatin administered at an initial area under the curve (AUC) of 1.5, and increased by an AUC of 0.5 per dose level to a maximum AUC of 3, corresponding with an AUC of 6 per cycle of chemotherapy. Radiation was administered in daily fractions of 200 cGy over 5-7 weeks. We treated 36 patients, of whom 27 had stage II or III disease, and nine had stage IV disease but required thoracic radiation for palliation. Toxicities included neutropenia (three with Grade 4) and esophagitis (seven with Grade 3 and one with Grade 4). Four patients had radiation pneumonitis 4-7 months after completing therapy, three of whom died. The recommended phase II dose of carboplatin is an AUC of 3 on 2 consecutive weeks. Of 33 patients evaluable for response within the radiation field, 17 (52%) had complete or partial response, and 13 had stable disease. Of seven patients evaluable with distant metastatic disease, three had a complete or partial response, and two had stable disease. The median survival for the entire group and for patients with stage II/III disease was 13.5 months. We conclude that the combination of carboplatin, vinorelbine, and radiotherapy is feasible at these doses. It may be a useful alternative for patients not able to tolerate cisplatin-based therapy.
Lung Cancer 2002 Oct
PMID:Carboplatin plus vinorelbine with concomitant radiation therapy in advanced non-small cell lung cancer: a phase I study. 1236 95

Platinum-based combination chemotherapy has become the standard treatment for good performance patients with stage IIIb and IV non-small cell lung cancer (NSCLC). However, newer agents such as gemcitabine and paclitaxel appear to have superior single agent activity and are more easily tolerated in comparison to the older platinum compounds. Therefore, we conducted this phase II study to evaluate the activity and toxicity of the combination paclitaxel and gemcitabine in advanced NSCLC. Gemcitabine was given at 1,000 mg/m(2) intravenously over 30 min followed by paclitaxel at 110 mg/m(2) intravenously over 1 h on days 1, 8 and 15 every 28 days for a maximum of 6 cycles. Between April 1998 and June 1999, 40 of 42 patients entered were eligible and received chemotherapy. Data was available on 39 patients. Toxicities included Grade 3/4 neutropenia in 43% of patients, while thrombocytopenia (13%) and anemia (7%) were less frequent. Five (12.5%) patients developed neutropenic fever. Four (10%) patients developed bilateral interstitial shadows with hypoxia suggestive of a drug-induced pneumonitis. There were 4 treatment-related deaths (1 from pneumonitis, 3 from neutropenic complications). Five patients were not evaluable due to early death. Therefore, 34 patients were evaluable with 12 (35.3%) achieving a partial remission and 1 achieving a complete remission for an overall response rate of 38.2% (32.5% on an intention-to-treat basis). The median progression free survival was 107 days (range, 14-391), median survival was 148 days (range, 12-495) and 1-year survival was 26%. In conclusion, weekly gemcitabine with paclitaxel in patients with advanced NSCLC is an active regimen; however, toxicity and poor survival precludes the use of this regimen as an experimental arm on a future phase III study.
Lung Cancer 2002 Oct
PMID:A phase II study of weekly gemcitabine and paclitaxel in patients with previously untreated stage IIIb and IV non-small cell lung cancer. 1236 96

Chemoradiation is standard treatment for patients with unresectable locally advanced non-small cell lung cancer (NSCLC). However, local and distant relapse rates remain high. It has been postulated that the addition of consolidation chemotherapy might further decrease the systemic relapse rate. We performed this phase II study to evaluate the toxicities and activity of two cycles of paclitaxel and carboplatin administered prior to and following thoracic radiation in patients with locally advanced, inoperable NSCLC. From April to December 1997, 25 patients were entered on study. Twenty-three patients were eligible and received paclitaxel 225 mg/m(2) intravenously over 3 h followed by carboplatin at an AUC (6) on days 1 and 22. Radiation consisted of 60 Gy given over 6 weeks beginning on day 43. Patients with non-progressive disease received two additional cycles of consolidation carboplatin and paclitaxel. Four of 23 patients progressed during induction chemotherapy. There were seven PR's and 11 had SD after induction chemotherapy. Following radiation, the response changed to 11 PR, four SD, and three had progressive disease. Of the 15 patients eligible to receive consolidation chemotherapy, three were excluded due to a poor performance status. Twelve patients were treated with consolidation chemotherapy with further improvement in two patients (SD to PR, PR to CR). All 12 patients who received consolidation chemotherapy developed grade 3 or 4 neutropenia, including three patients with neutropenic fever. The overall response rate was 52.1%. The median survival, 1-, and 2-year survival was 10.5 months, 45, and 17%, respectively. In conclusion, consolidation chemotherapy was associated with significant hematologic toxicity without an obvious improvement in survival in comparison to other studies utilizing chemoradiation alone.
Lung Cancer 2002 Oct
PMID:Carboplatin plus paclitaxel and sequential radiation followed by consolidation carboplatin and paclitaxel in patients with previously untreated locally advanced NSCLC. A Hoosier Oncology Group (HOG) phase II study. 1236 98

Recent experience with weekly administration of docetaxel has demonstrated less myelotoxicity and suggested that this regimen holds promise for elderly patients at the high risk of myelosuppression. However, in this phase I trial of weekly docetaxel conducted only in elderly patients (70 years old or more) with non-small cell lung cancer (NSCLC), the toxicity profile was markedly different from that in previous reports. The dose-limiting toxicities were neutropenia, diarrhea and infection, all of which were observed at a dose of 30 mg/m(2)/week and the maximum-tolerated dose by protocol definition was 30 mg/m(2)/week. Although other hematological and non-hematological toxicities observed in this treatment were generally moderate and were well tolerated by elderly patients with NSCLC, the risk of myelosuppression still requires careful attention.
Lung Cancer 2002 Nov
PMID:Phase I trial of weekly docetaxel in elderly patients with non-small cell lung cancer. 1239 34

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.
Lung Cancer 2002 Dec
PMID:Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer. 1244 53

Docetaxel and vinorelbine as single agents and in combination with cisplatin have shown significant activity in advanced non-small cell lung cancer (NSCLC). Significant neutropenia has been observed with the combination of docetaxel/vinorelbine. To gain insight into the potential synergism of this combination, we examined three different sequences of docetaxel 75 and vinorelbine 20 mg/m(2), every 3 weeks, in locally advanced and metastatic NSCLC patients. About 14 patients were evaluable in each schedule: schedule A, docetaxel day 1, vinorelbine days 1 and 6; schedule B, docetaxel day 6, vinorelbine days 1 and 6; schedule C, docetaxel day 1, vinorelbine days 6 and 15. Response rates were: 42.8, 7.1 and 21.4% for schedules A, B and C, respectively (P=0.01, schedule A vs. B). Median survival time was 16, 6.5 and 10.6 months for schedules A, B and C, respectively (P=0.04, schedule A vs. B). Neutropenia was the commonest toxicity; 43% of patients in schedule A and 57% of patients in schedule B had a febrile neutropenia episode. Prophylactic granulocyte-colony stimulating factor (G-CSF) was prescribed in schedule C after the first episode of febrile neutropenia. Non-hematologic toxicities were mild in all three schedules. For future studies, schedule A with lower doses is recommended.
Lung Cancer 2002 Dec
PMID:Phase II non-randomized study of three different sequences of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer. 1244 54


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