Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.
Lung Cancer 1998 Sep
PMID:Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer. 985 99

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

The combination of carboplatin and paclitaxel is an active regimen in non-small cell lung cancer (NSCLC). Historically, patients with stage III disease have manifested higher response rates than patients with metastatic disease, and patients achieving a pathologic complete response to induction chemoradiation therapy prior to surgery have shown better long-term outcome. Based upon our pilot data using high-dose carboplatin and paclitaxel, we designed a phase II trial in patients with marginally resectable stage IIIA NSCLC. Ten patients, with bulky nodal stage IIIA disease, initially received etoposide (2 g/m2) and granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC). Two cycles, 28 days apart, of carboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitaxel (250 mg/m2) were administered with filgrastim (5 microg/kg) and PBSC support. After re-evaluation, patients underwent a thoracotomy followed by radiotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG performance status of 0 (0-1). Histology was adenocarcinoma in seven patients; the remainder had either squamous cell, large cell or bronchoalveolar carcinoma. Based on CT radiography, the overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies, three right upper lobectomies and one wedge resection of the right upper lobe. Six patients had a complete resection. Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metastatic disease while receiving chemotherapy. The median dose of postoperative radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patients was 89 weeks (25 to 136+). The actuarial median overall survival was 124 weeks (25 to 136+) and time to progression was 57 weeks (17 to 136+). The median dose of carboplatin delivered expressed as mg/m2 was 779 (615-1540). Neutropenic fever occurred in two patients during the initial mobilization cycle only. The median number of units of RBC and/or platelets transfused was 0 (0-2 and 0-6, respectively). There were no significant non-hematologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, including pneumonectomy and postoperative radiotherapy, were well tolerated by patients after undergoing high-dose induction chemotherapy with no apparent increase in peri-operative morbidity. The pathologic complete response rate was low--one out of ten patients. These results indicate that dose escalation of induction chemotherapy does not improve response rates even in this highly selected patient population. Accordingly, the complexity and potential toxicity of high-dose chemotherapy, as delivered in this trial as neoadjuvant treatment of non-small cell lung cancer, is not warranted.
Lung Cancer 2000 Jan
PMID:Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung. 1067 82

Photofrin-based photodynamic therapy (PDT) has recently been approved for palliative and curative purposes in cancer patients. It has been demonstrated that neutrophils are indispensable for its anti-tumour effectiveness. We decided to evaluate the extent of the anti-tumour effectiveness of PDT combined with administration of granulocyte colony-stimulating factor (G-CSF) as well as the influence of Photofrin and G-CSF on the myelopoiesis and functional activity of neutrophils in mice. An intensive treatment with G-CSF significantly potentiated anti-tumour effectiveness of Photofrin-based PDT resulting in a reduction of tumour growth and prolongation of the survival time of mice bearing two different tumours: colon-26 and Lewis lung carcinoma. Moreover, 33% of C-26-bearing mice were completely cured of their tumours after combined therapy and developed a specific and long-lasting immunity. The tumours treated with both agents contained more infiltrating neutrophils and apoptotic cells then tumours treated with either G-CSF or PDT only. Importantly, simultaneous administration of Photofrin and G-CSF stimulated bone marrow and spleen myelopoiesis that resulted in an increased number of neutrophils demonstrating functional characteristics of activation. Potentiated anti-tumour effects of Photofrin-based PDT combined with G-CSF observed in two murine tumour models suggest that clinical trials using this tumour therapy protocol would be worth pursuing.
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PMID:Potentiation of the anti-tumour effects of Photofrin-based photodynamic therapy by localized treatment with G-CSF. 1078 May 31

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

This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.
Lung Cancer
PMID:A phase I/II trial of cisplatin, docetaxel and ifosfamide in advanced or recurrent non-small cell lung cancer. 1155 21

The combination of IP (irinotecan/cisplatin) has been shown to confer a survival benefit compared with EP (etoposide/cisplatin) in patients with extensive-stage small-cell lung cancer (SCLC). Based on this and potential synergy from sequential inhibition of topoisomerases I and II, we conducted a phase I study to assess the feasibility of weekly therapy alternating IP and EP. The doses of EP were fixed (etoposide 60 mg/m2 on days 1-3 and cisplatin 20 mg/m2 on day 1). The dose of irinotecan was escalated in serial cohorts at 3 dose levels: 80, 90, and 100 mg/m2 on day 1. Granulocyte colony-stimulating factor was given on days 2-5 and days 4-7 after IP and EP, respectively. Patients with limited-stage SCLC received chemoradiation during weeks 4-6 with etoposide 120 mg/m2 on days 1-3, cisplatin 60 mg/m2 on day 1, and thoracic radiation 1.5 Gy twice daily in 30 fractions. Patients received 12 weeks of therapy. To evaluate dose escalation in subsequent cohorts, dose-limiting toxicity (DLT) was initially assessed during weeks 1-3 of treatment. Characteristics of the 18 patients accrued are as follows: performance status 0/1, n = 9; female sex, n = 9; extended-stage SCLC, n = 16; and median age, 53 years. Four patients treated at irinotecan dose level 1 (80 mg/m2), 6 patients at dose level 2 (90 mg/m2), and 6 patients at dose level 3 (100 mg/m2) did not experience DLT in weeks 1-4 and completed therapy without major incident. The only 2 patients to experience DLT during weeks 1-4 were treated at dose level 2. Both were hospitalized during week 4 and subsequently died. However, patients had already been accrued at dose level 3 and tolerated therapy well. Therefore, the trial design was modified to assess DLT during weeks 1-4, and additional patients were cautiously added to the dose level 2 and 3 cohorts. Analysis of summary toxicity data resulted in a recommendation that dose level 3 be used in phase II based on the probability of DLT of 16% (95% CI, 3%-29%). Responses in 16 evaluable patients include complete response in 1 patient, partial response in 14 patients, and minor response in 1 patient. With the exception of the 2 deaths, the therapy was well tolerated and active. Phase II evaluation of the regimen in patients with extensive-stage SCLC is ongoing.
Clin Lung Cancer 2003 Jul
PMID:Phase I study of weekly alternating therapy with irinotecan/cisplatin and etoposide/cisplatin for patients with small-cell lung cancer. 1459 3

The purpose of this study was to compare the efficacy and safety profile of docetaxel versus the combination of docetaxel/cisplatin as frontline treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) in a multicenter, randomized, prospective phase III trial. Patients with unresectable stage IIIB or metastatic stage IV NSCLC who had previously undergone no chemotherapy were allocated to receive either docetaxel (100 mg/m2 in a 1-hour intravenous infusion; group A) or the combination of docetaxel (100 mg/m2 day 1) and cisplatin (80 mg/m2 day 2) after adequate hydration (group B). Appropriate premedication was given before docetaxel infusion. All patients in group B received granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) support from days 3 to 9 after treatment. Response and toxicity were assessed by World Health Organization criteria. From March 1999 to November 2001, 302 patients were randomly assigned to receive docetaxel (group A, n = 146) or docetaxel/cisplatin (group B, n = 156). The overall response rate was significantly higher in the combination arm (18% vs. 36%; P < 0.001). However, the 2 groups did not differ in median duration of response, time to progression (TTP), median overall survival (OS), or 1-year survival rate. Drug combination was associated with higher toxicity than single-agent therapy. Both regimens had comparable activity in terms of TTP and OS in chemotherapy-naive patients with advanced NSCLC; however, single-agent therapy had a more favorable toxicity profile.
Clin Lung Cancer 2003 Mar
PMID:Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study. 1460 46

Preoperative chemotherapy in patients with stage III non-small-cell lung cancer (NSCLC) remains controversial. Phase II trials utilizing preoperative chemotherapy in selected patients have achieved complete resection rates of 50%-70% with 3-5 year failure-free survival rates of 15%-33%. Between October 1992 and November 1994, 57 adults (50 of whom were evaluable) with surgically staged IIIA NSCLC and pathologically documented ipsilateral mediastinal nodal involvement (N2) were enrolled in a Cancer and Leukemia Group B randomized trial. Preoperative therapy was thought to be critical to facilitating surgical resectability. For patients randomized to the radiotherapy/surgery/radiotherapy (RSR) arm (n = 24), treatment consisted of preoperative radiation therapy (RT) at 40 Gy, surgery, and then additional RT at 14-20 Gy. For patients randomized to the chemotherapy/surgery/chemotherapy/radiotherapy (CSCR) arm (n = 26), treatment consisted of 2 cycles of cisplatin/etoposide with filgrastim support (PE) followed by surgery, 2 more cycles of PE, then RT 54-60 Gy. The total dose of RT on either arm was 54 Gy if completely resected or 60 Gy if incompletely resected or unresected. Clinical characteristics were well balanced between the two arms. Thoracotomy was performed in 42 patients (84%), 28 (67%) of whom had complete resection. The median failure-free and overall survival rates were 12 months (95% confidence interval [CI], 9-23 months) and 23 months (95% CI, 19 months-infinity) for the RSR arm and 11 months (95% CI, 5-20 months) and 18 months (95% CI, 12-32 months) for the CSCR arm. The rates of overall and complete surgical resection, downstaging of nodal involvement, and failure-free (P = 0.92) and overall survival (P = 0.41) did not differ between the two treatment arms. Moreover, in this trial, the chemotherapy regimen was sufficiently toxic to have had a lower completion rate of prescribed therapy in the CSCR arm than in the RSR arm.
Clin Lung Cancer 2002 Sep
PMID:Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2 non-small-cell lung cancer. 1465 65

The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss <or= 5%, and primarily stage IIIB or bulky IIIA NSCLC. Induction chemotherapy (CT), 2 cycles of paclitaxel 175-225 mg/m2 over 3 hours and carboplatin (targeted area under the curve [AUC] of 7.5), was administered on days 1 and 22. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was given on days 2-15 and 23-36 to all patients; half were randomized to priming G-CSF every day x 5 prior to day 1 of induction therapy. On day 43, TRT (60-63 Gy/30-34 fx) was initiated. At dose level 1, only Fox Chase Cancer Center patients received carboplatin (initial target AUC 3.75) and paclitaxel (67.5 mg/m2 over 3 hours) days 43 and 64. In the absence of dose-limiting toxicity, phase I dose escalation in 3-patient cohorts was scheduled to proceed to a maximum carboplatin AUC 7.5 and paclitaxel dose of 210 mg/m2. To date, 53 patients have received induction therapy; 4 are too early to evaluate. The portion of the study evaluating G-CSF priming revealed no myeloprotective effect, likely due to a lack of myelosuppressive toxicity with the conventionally dosed cohort. Twenty-two patients have received concurrent TRT/CT. In sequential cohorts, the chemotherapy doses on days 43 and 64 have been escalated (to paclitaxel 175 mg/m2 and carboplatin AUC 5) with 1 episode each of grade 4 granulocytopenia and grade 3 anemia. The occurrence of grade >or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.
Clin Lung Cancer 2001 Nov
PMID:Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report. 1465 27


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