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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the efficacy and toxicity of a brief, intensive cisplatin-based outpatient chemotherapy regimen with filgrastim and megestrol acetate support for patients with stage IIIB and IV non-small cell lung cancer (NSCLC) and a favorable performance status. Thirty patients with no prior chemotherapy were enrolled in this phase II protocol. Patients received cisplatin 50 mg/m2, ifosfamide 2 g/m2, mesna, and a 7-day course of oral etoposide beginning on days 1, 15, 29, 43. and 57 for a total treatment duration of 10 weeks. Filgrastim was administered for 7 days after each course of oral etoposide. Megestrol acetate 250 mg PO was administered throughout the duration of chemotherapy. Thirty patients were evaluable for toxicity and 27 for response. Among those evaluable for response, partial remission occurred in 11 (41%) patients, and median survival was 10.5 months. Nadir neutrophil count of < 500/mm3 occurred in 19 (63%) patients. Weight loss occurred in only nine patients (median 3.4 kg, range 1.6-7.3). There was no difference between pre- and post-treatment weights (P=0.35). Two patients developed pulmonary embolism. Grade 3 or 4 non-hematologic toxicity occurred infrequently. This regimen appears to be similar in efficacy to the most active regimens reported by other investigators. Innovative features of the regimen include the brief treatment duration, the use of serial 7-day courses of filgrastim to facilitate weekly chemotherapy treatments, and the use of megestrol acetate to minimize constitutional symptoms. However the use of megestrol acetate in this setting may be associated with an increased risk of thromboembolic complications. This may provide a model for other palliative regimens specifically designed for patients with a favorable performance status and advanced NSCLC.
Lung Cancer 1998 Dec
PMID:A brief intensive cisplatin-based outpatient chemotherapy regimen with filgrastim and megestrol acetate support for advanced non-small cell lung cancer: results of a phase II trial. 1004 75

An interim report evaluating the feasibility of myeloablative therapy followed by peripheral blood stem cell (PBSC) autotransplant in patients aged >60 years is presented. In the last 2 years 19 patients >60 years old with several oncological conditions, mostly hematological, underwent PBSC autotransplant either as salvage therapy following relapse or resistance to conventional treatment, or as consolidating therapy as a part of a well defined protocol. There were 13 males and six females; the mean age was 66.9 years (range 61-76 years); nine patients had resistant or relapsed lymphoma, six myeloma, two acute leukemia, one Waldenstrom's disease and one lung cancer. Myeloablative schemes included BEAM exclusively for lymphomas, busulfan and melphalan (Bu-MPH) mainly for myeloma, busulfan and cyclophosphamide (Bu-CTX) for lymphomas and leukemia and VP-16 and CTX for lung cancer. Mobilization of CD34+ cells was achieved in all patients with the combination of high-dose CTX and G-CSF with collections between 2.83 to 19.04 x 10(6)/kg (mean 7.1). All patients engrafted with a median time for recovery of PMN (>0.5 x 10(3)/microl) of 10 days (range 8-12 days) and for PLT (>20 x 10(3)/microl) of 12 days (range 10-17 days). Major responses were obtained in 15 of 16 patients evaluable for response and eight patients entered CR; overall eight patients are in CR, five are alive with disease, five are dead from disease progression and one is dead because of congestive heart failure 7 months following PBSC autotransplant. No early deaths following the procedure occurred; major side-effects were grade I-II mucositis (58%), fever with documented sepsis (10%), pneumonia (5%), cardiac, renal and liver toxicity (5%). Cardiac function was evaluated before and after myeloablative therapy by VEF in all patients; no significant modifications were necessary. In conclusion, our experience demonstrates that myeloablative therapies in older selected patients can be feasible; the feasibility of introducing PBSC autotransplantation following myeloablative therapy as a front-line treatment in patients aged >60 years, needs accurate guide lines for selection of appropriate patients.
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PMID:Analysis of feasibility of myeloablative therapy and autologous peripheral stem cell (PBSC) transplantation in the elderly: an interim report. 1041 15

Paclitaxel is an antimicrotubule agent that interferes with cell division. It has demonstrated promising single-agent activity against non-small-cell lung cancer. The purpose of this study was to evaluate the therapeutic effectiveness of paclitaxel in previously untreated patients with extensive stage small-cell lung cancer (SCLC). The study was designed as a two-stage phase II trial. All patients who entered received paclitaxel by intravenous infusion at a dose of 250 mg/m2 during 24 hours. Granulocyte colony stimulating factor was also provided to ameliorate neutropenia. Cycles were repeated at 21-day intervals. Patients who achieved a complete response received a maximum of 10 cycles of treatment, whereas those who achieved a partial response/regression continued treatment until progression or undue toxicity developed. Patients who progressed or maintained stable disease for six cycles were crossed over to cisplatin and etoposide. Forty-three patients entered the study and all were evaluable for analysis. Responses were observed in 23 (53%) of the patients. There was no significant difference in the response rates in patients with measurable or evaluable disease (13/23 versus 10/20, p = 0.76). At the time of analysis, 39 patients had progressed with a median time to progression of 95 days, and 39 patients had died with a median survival of 278 days. The 1-year achieved survival rate was 24%. Significant neutropenia (absolute neutrophil count <1,000/microl) occurred in 24 (56%) of the patients, but only 2 patients experienced severe infection (grade > or = 3), and there were no septic deaths. The results indicate that paclitaxel is active against SCLC. Myelosuppression was the main side effect in this patient population. Response duration was short (median = 3.4 months), which suggests that paclitaxel is not sufficient as a single agent. Further studies of paclitaxel in combination with other agents against SCLC are currently in progress within the North Central Cancer Treatment Group and other cancer treatment groups. Key Words: Paclitaxel-G-CSF-Small-cell lung cancer-North Central Cancer Treatment Group.
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PMID:Paclitaxel and G-CSF in previously untreated patients with extensive stage small-cell lung cancer: a phase II study of the North Central Cancer Treatment Group. 1052 Oct 70

A prospective phase II study was conducted to determine the response, toxicity and survival rate of lung cancer patients treated with combination paclitaxel and carboplatin in stage IIIB and IV NSCLC. Eligible patients required measurable and/or evaluable diseases; performance status (ECOG) 0-2; no previous chemotherapy; adequate hepatic, renal and bone marrow function. Paclitaxel was administered at a dose of 200 mg/m2, 3 h infusion, followed by carboplatin at an AUC of 6. Treatment was repeated every 3 weeks for six courses. G-CSF 5 microgram/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leucopenia or granulocytopenia in the previous course. From April 1996 through July 1997, 53 patients were enrolled; all are assessable for toxicity and response. The median age was 56 years (range, 20-77 years). Sixty four percent were male, 64% had adenocarcinoma and 62% had stage IV disease. Two hundred and seventy two courses were administered; 36 patients (68%) completed all six cycles. Two patients achieved a complete response (4%) and 27 patients achieved a partial response (51%), for an overall response rate of 55%. Sixteen patients had stable disease (30%) and 8 patients had progressive disease (15%). The median progression free survival time for all patients, stage IIIB and stage IV patients was 28 weeks (range, 18-37 weeks), 31 weeks (range 21-41 weeks) and 22 weeks (range 16-29 weeks), respectively. The median survival time and 1 year survival rate for all patients was 55 weeks (range, 51-59 weeks) and 55%, respectively. Stage IIIB patients had better median survival time and 1-year survival rate than stage IV patients (75 vs. 46 weeks, P = 0.007; 80% vs. 42%, P = 0.003). Grade 3 and 4 granulocytopenia, anemia and thrombocytopenia were observed in 25, 3, and 1%, respectively, of the 272 courses administered. G-CSF was required in 28% of the 272 courses. There were four episodes of febrile neutropenia (1.5%), three episodes of angina pectoris (1%) and one episode of anaphylaxis (0.4%). Other common toxicities, generally mild, included myalgia, arthralgia, peripheral neuropathy and asthenia. Most toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.
Lung Cancer 1999 Dec
PMID:Phase II study of paclitaxel and carboplatin for advanced non-small-cell lung cancer. 1059 28

A 73-year-old man was hospitalized because of weight loss and fever. Laboratory data showed marked leukocytosis (21,200/mm3), granulocytosis (89.7%), thrombocytosis (47.8 x 10(4)/mm3), increased CRP (15.8 mg/dl), and increased SCC (5.0 ng/ml). Chest X-ray films demonstrated a mass shadow in the right upper lung field. Chest computed tomographic scans revealed a mass shadow 58 mm in diameter with mediastinal pleural invasion in the right S1. Right upper lobectomy and dissection of regional lymph nodes was performed under a diagnosis of lung cancer (squamous cell carcinoma, T3 N0 M0 stage IIB) with concomitant infection. Serum G-CSF was 234 pg/ml pre-operatively and 68.8 pg/ml postoperatively. The cytoplasm of tumor cells stained positively with anti-recombinant human G-CSF monoclonal antibody. No general bacteria or mycobacteria were detected within the specimen. Postoperatively, the patient's white blood cell count, platelet count, and CRP level soon decreased, and the fever disappeared. We diagnosed the disease as G-CSF-producing squamous cell type lung cancer.
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PMID:[Squamous cell type lung cancer that produced granulocyte colony-stimulating factor]. 1092 Dec 88

This phase III study was conducted to evaluate the usefulness of lenograstim as support for ACE (doxorubicin, cyclophosphamide, and etoposide) chemotherapy in previously untreated patients with small-cell lung cancer. Patients were randomized to receive up to six 3-week cycles of either ACE alone (n = 139) or ACE with lenograstim support (150 microg/m2/day subcutaneously, days 4-13, n = 141). Compared with the chemotherapy-alone group, the lenograstim support group was more likely to achieve neutrophil recovery (absolute neutrophil count, > or =1.5 x 10(9) cells/l) by day 14 (95.8-100% vs. 14.3-24.1% across the cycles) and less likely to experience at least one infectious episode (36.7 vs. 54.0%; p = 0.004), chemotherapy delay (51.8 vs. 56.2%; NS), or dose reduction (17.3 vs. 27.7%; p = 0.037). Objective response and event-free and overall survival rates were similar. Lenograstim was well tolerated. Lenograstim may allow the interval between cycles of ACE to be reduced to 2 weeks; such dose intensification may lead to more favorable objective response and survival rates.
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PMID:Lenograstim as support for ACE chemotherapy of small-cell lung cancer: a phase III, multicenter, randomized study. 1095 71

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
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PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

Obtaining a complete response (CR) is the most powerful predictor of survival in extensive-stage small cell lung cancer (SCLC). Improvements in long-term survival in extensive-stage SCLC can be made if the proportion of complete responders to induction therapy can be increased. We performed a phase II trial of the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP regimen) in extensive-stage SCLC. The primary endpoint for this trial is the proportion of patients (pts) obtaining a CR rather than overall response. The null hypothesis for this trial consists of the absence of a CR rate >20%. Paclitaxel was given at doses of 135 (3 pts) or 170 mg/m(2) i.v. over 3 h on day 1. Cisplatin 60 mg/m(2) was given on day 1. On days 1-3 etoposide 80 mg/m(2) per day i.v. was given. G-CSF was used from days 5 to 14 of each cycle. Cycles were repeated q21 days. A two-stage design was used for patient accrual, based on the occurrence of complete responses. Initially, 16 patients were to be accrued. If more than three complete responses were to occur, a further 20 patients would be accrued to the study (Simon's optimal two stage design). Sixteen patients were enrolled. Two patients had a CR (13%) and nine patients had a partial response (56%) for an overall response rate of 69%. The trial was suspended due to the low CR rate. Review of the literature for paclitaxel based front-line treatment combined with EP therapy, in extensive stage SCLC, consistently shows a CR rate <20% but high overall response rate is maintained (thus most responses are partial). As virtually all long-term survivors in extensive-disease SCLC have had a CR to induction therapy and CR remains the strongest predictor of survival for this disease, this may suggest that paclitaxel added to standard EP may improve progression-free survival (and possibly median survival) but is unlikely to significantly improve long-term survival. Initial randomized phase III data confirm the absence of impact on survival for this triple-drug regimen compared to EP therapy alone. Furthermore, other regimens comparing favorably to the EP regimen have all shown consistent CR rates >20% in the phase II setting. In conclusion, consideration should be given to the use of CR rate as a phase II endpoint to determine if a particular regimen should be compared to the standard in a phase III setting for extensive-stage SCLC. A two-stage phase II design based on a minimum required completed responses for further patient accrual is recommended.
Lung Cancer 2001 May
PMID:Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials. 1132 86

Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.
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PMID:Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients. 1140 6

It is generally believed that elderly patients are less able to tolerate aggressive cancer chemotherapy than their younger counterparts. Bone marrow cellularity diminishes with age and elderly patients may have decreased tolerance to myelosuppressive agents. Between November 1995 and October 1999, 68 chemotherapy-naive elderly (70 or more years old) patients with histologically or cytologically proven lung cancer who were to receive platinum-based chemotherapy were enrolled in this study. All patients had adequate cardiac, hematological, liver and renal function to receive chemotherapy. Patients were randomized into 3 groups. Patients in groups 1 and 2 received 2 microg/kg and 4 microg/kg granulocyte colony-stimulating factor (G-CSF, lenograstim), respectively, when grade 3 leukopenia (<2,000/microl) or neutropenia (<1,000/microl) appeared after chemotherapy. Patients in group 3 received 2 microg/kg G-CSF when grade 2 leukopenia (<3,000/microl) or neutropenia (<1,500/microl) appeared after chemotherapy. G-CSF was stopped in all groups when the leukocyte count increased to over 10,000/microl or the neutrophil count exceeded 5,000/microl. Full blood cell counts were examined 3 times a week after chemotherapy. All patients received platinum-based chemotherapy. Eighteen, 16 and 22 patients (78%, 73% and 96%) in groups 1, 2 and 3, respectively, received G-CSF when leukopenia or neutropenia appeared. The durations of G-CSF treatment required by groups 1 and 3 (5.7+/-3.6 and 6.6+/-3.2 days, respectively) did not differ significantly, but the duration of treatment required by group 2 (3.7+/-2.8 days) was significantly shorter than that of group 1 (p=0.048). The duration of grade 4 neutropenia in group 2 (0.7+/-1.1 days) was marginally shorter than that in group 1 (1.6+/-2.1 days, p=0.076). The neutrophil nadir of group 2 (949+/-757/microl) was marginally higher than that of group 1 (592+/-438/microl, p=0.058). No patients in group 2 experienced grade 4 neutropenia for 4 days or more or a neutrophil nadir less than 100/microl a significant difference from group 1, where 22% and 17% of patients experienced these events (p=0.02 and p=0.04, respectively). Similarly, no infections requiring antibiotics after chemotherapy occurred in patients in group 2, a significant difference from group 1 (26%, p=0.01). The rates of neutropenia and infection in groups 1 and 3 did not differ significantly. The peak plasma concentration of G-CSF in group 2 was significantly higher than in group 1 (p=0.0018), but did not differ significantly between groups 1 and 3. Doubling the dose of G-CSF could help to decrease neutropenia and prevent infection after chemotherapy in elderly patients with lung cancer.
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PMID:Randomized study of dose or schedule modification of granulocyte colony-stimulating factor in platinum-based chemotherapy for elderly patients with lung cancer. 1141 Jul 99


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