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1.
M. Gatineau E. Dansin F. Chomy E. Lemarie P. Nouyrigat S. Oudard R. Mouawad A. Tisseron Carrasco D. Khayat O. Rixe 《Targeted oncology》2006,1(3):114-122
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib and the cytotoxic agent docetaxel are both used for the second-line treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of gefitinib in combination with docetaxel within this disease setting, and to evaluate the predictive value of assessing pre-treatment levels of soluble serum EGFR and HER2. In this open-label, non-comparative, multicenter, phase II trial, patients with non-resectable advanced or metastatic NSCLC were treated with oral gefitinib (250 mg/day) in combination with docetaxel (75 mg/m2 IV every 3 weeks). Forty-eight patients were enrolled: 30 had progressed during or after platinum-based chemotherapy (Group A) and 18 were unsuitable for platinum-based chemotherapy (Group B). Anti-tumor activity was seen with objective response rates of 23.3% (Group A) and 11.8% (Group B). The most frequent adverse events considered to be gefitinib-related were diarrhea (57.4%) and skin-related events (dry-skin: 31.9%; rash: 29.8%; pruritus: 12.8%), and those considered to be docetaxel-related were alopecia (21.3%), nausea (19.1%), and diarrhea (17.0%). The addition of gefitinib did not seem to affect the hematological toxicity seen with docetaxel. Serum biomarker investigations revealed that patients who responded had lower serum EGFR levels than non-responders, although this association was not significant (p=0.07). In conclusion, the combination of gefitinib with docetaxel was feasible, generally well tolerated, and has activity for the treatment of advanced NSCLC. Soluble serum EGFR (and HER2 levels) did not appear to be predictive for response. Although this study confirms that the combination of gefinitib and docetaxel appears promisingly effective and tolerable, it should not be recommended as a standard option for second-line therapy in non-small cell lung cancer until results from phase III trials showing a significant superiority over docetaxel alone are available. 相似文献
2.
Sym SJ Chang HM Kang HJ Lee SS Ryu MH Lee JL Kim TW Yook JH Oh ST Kim BS Kang YK 《Cancer chemotherapy and pharmacology》2008,63(1):1-8
Purpose Irinotecan (I) and docetaxel (D), each of which has a unique mechanism of action, were recently introduced in the treatment
of patients with advanced gastric cancer (AGC). We have evaluated the efficacy and safety of the ID combination for AGC patients
after failure of fluoropyrimidine- or platinum-based chemotherapy.
Materials and methods Patients with relapsed or progressive AGC after prior fluoropyrimidine- or platinum-based chemotherapy were treated with I
(160 mg/m2, 90 min) followed by D (65 mg/m2, 1 h) every 3 weeks. Because of the unacceptable toxicity among the first ten patients, the doses were reduced for I (120 mg/m2) and D (50 mg/m2) every 3 weeks.
Results Forty-nine patients, of median age 53 years (range, 27–68 years), were treated with 170 cycles of chemotherapy (median, 2
cycles; range, 1–12 cycles). Three patients achieved complete response and seven achieved partial response, resulting in an
overall response rate (ORR) of 20.4% [95% confidence interval (CI), 9.1–31.7%], with a median duration of 7.1 months (range:
2.1–69.1 months). ORR was 60% (95% CI, 29.6–90.3%) for the higher dose and 10.3% (95% CI, 0.7–19.8%) for the lower dose. Median
time to progression for all patients was 2.7 months (95% CI, 1.7–3.8 months) and the median overall survival was 8.9 months
(95% CI, 6.6–11.3 months). Grade 3/4 toxicities included neutropenia (90%), febrile neutropenia (50%), asthenia (40%), and
diarrhea (10%) with the higher dose and neutropenia (71%), febrile neutropenia (11%), diarrhea (24%), and asthenia (24%) with
the lower dose. There were two possible treatment-related deaths.
Conclusion The combination of irinotecan and docetaxel, once every three weeks shows anti-tumor activity but is not feasible as a second-line
treatment for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy due to the high rate of toxicities.
S. J. Sym and H. M. Chang
have contributed equally to this article. 相似文献
3.
Casal J Amenedo M Mel JR Antón LM Rodríguez-López R López-López R González-Ageitos A Castellanos J Constenla M Tisaire JL 《Cancer chemotherapy and pharmacology》2007,60(5):725-732
Background Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules
against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy.
Methods This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m2 (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m2 (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC.
Results Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182
chemotherapy cycles (median 6, range 1–6) was administered to 40 patients during the study; one patient did not receive chemotherapy
due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44%
(95% CI, 29–59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration
of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and
the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except
for pulmonary toxicity. The main grade 3–4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases
of febrile neutropenia were reported. The main grade 3–4 non-hematological toxicity was pulmonary toxicity (23% of patients,
6% of cycles).
Conclusion Gemcitabine 1,000 mg/m2 on days 1 and 8 in combination with docetaxel 85 mg/m2 on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC. 相似文献
4.
Kosmas C Tsavaris N Syrigos K Koutras A Tsakonas G Makatsoris T Mylonakis N Karabelis A Stathopoulos GP Kalofonos HP 《Cancer chemotherapy and pharmacology》2007,59(1):51-59
Purpose: Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I–II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC. Patients and methods: Patients with advanced NSCLC, WHO-performance status (PS) ≤ 2, prior taxane/platinum-based chemotherapy were eligible. Chemotherapy was administered in a dose-escalated fashion in subgroups of 3–6 patients until dose-limiting toxicity (DLT) was encountered as follows: CPT-11 150 or 180 mg/m2 followed by GEM 1,200–1,800 mg/m2, both on days 1 + 15, recycled every 28 days in four dose levels (DLs). Results: Forty-nine patients entered the phase I and II part of the study (phase I: 12–phase II: 37 + 3 at DL-3), and 40 patients were evaluable for a response in phase II and all for toxicity: median age, 61 years (range 36–74); PS, 1 (0–2); gender, 43 males/6 females—histologies; adenocarcinoma, 25; squamous, 20; large cell, 4. Metastatic sites included lymph nodes, 38; bone, 5; liver, 4; brain, 3; lung nodules, 14; adrenals, 13; other, 3. All patients had prior taxane + platinum-based treatment, and 42 patients had prior docetaxel–ifosfamide–cisplatin/or–carboplatin regimens. DLT was observed at DL-4 and included 2/3 cases with grade 3 diarrhea—1/3 of these with febrile neutropenia. The recommended DL for phase II evaluation was DL3: GEM, 1,500 + CPT-11—180 mg/m2. Objective responses in phase II were PR, 6/40 [15%; 95% confidence interval (CI), 5–31%]; stable disease, 16/40 (40%; 95% CI, 21–53%); and progressive disease, 18/40 (45%; 95% CI, 28.5–62.5%). The median time-to-progression was 4 months (range 1–12) and median survival 7 months (range 1.5–42 +), while 1-year survival was 20%. Grade 3/4 neutropenia was seen in 18% of patients (6% grade 4) and 6% incidence of febrile neutropenia. No Grade 3/4 thrombocytopenia were seen, grade 3 diarrhea in 6% of patients and grade 2 in 15% of patients, while other grade 3 non-hematologic toxicities were never encountered. Conclusions: Bi-weekly GEM + CPT-11 is active and well tolerated in patients with advanced NSCLC failing prior taxane + platinum regimens, and represents an effective and convenient combination to apply in the palliative treatment of relapsed NSCLC particularly after failure of first-line docetaxel + platinum-based regimens. 相似文献
5.
U.S. Food and Drug Administration Approval Summary: Ramucirumab for the Treatment of Metastatic Non‐Small Cell Lung Cancer Following Disease Progression On or After Platinum‐Based Chemotherapy
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Erin Larkins Gideon M. Blumenthal Erik Bloomquist Shenghui Tang Missiratch Biable Paul Kluetz Patricia Keegan Richard Pazdur 《The oncologist》2015,20(11):1320-1325
On December 12, 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab. This approval was based on an improvement in overall survival (OS) with an acceptable toxicity profile in a randomized, multicenter, double-blinded, placebo-controlled trial of 1,253 patients with metastatic NSCLC previously treated with a platinum-based combination therapy. Patients were randomized 1:1 to receive either ramucirumab in combination with docetaxel or placebo in combination with docetaxel. The primary endpoint was OS. Patients who received ramucirumab in combination with docetaxel had improved OS (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.75, 0.98). Median OS was 10.5 months on the ramucirumab plus docetaxel arm versus 9.1 months on the placebo plus docetaxel arm. The most frequent (≥30%) adverse reactions in ramucirumab-treated patients were fatigue, neutropenia, and diarrhea. The most frequent (≥5%) grade 3 and 4 adverse reactions in the ramucirumab arm were fatigue, neutropenia, febrile neutropenia, leukopenia, and hypertension.
Implications for Practice:
This report presents key information on the U.S. Food and Drug Administration approval of ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2, given in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer whose disease has progressed on or after platinum-based chemotherapy. This report specifically addresses the issues of safety in patients with squamous cell tumors, effect of treatment in elderly patients, and uncertainties regarding effects in patients with tumors harboring epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations. 相似文献6.
Oscar Arrieta Cynthia Villarreal-Garza Digna Pachuca Rosa M. Michel Ortega Luis Martinez-Barrera Diana Flores-Estrada Alma Astorga 《Medical oncology (Northwood, London, England)》2011,28(1):300-306
Because of improved therapeutic results after first-line platinum-based chemotherapy in patients with stage IV non-small-cell
lung cancer (NSCLC), second-line chemotherapy may be considered for a growing number of patients. Approximately, 10% of patients
have an interval time after concluding first-line platinum-based chemotherapy greater than 6 months. These patients may achieve
high tumor responses when platinum is again used in second-line treatment. Twenty-three patients experiencing progression
following 6 months after concluding platinum-based chemotherapy were managed with second-line treatment with carboplatin combined
with gemcitabine or pemetrexed. Overall response, progression-free survival (PFS), and overall survival (OS) after initiation
of second-line treatment were calculated for all patients. Median PFS after first-line treatment was 12.6 months (95% confidence
interval [95% CI], 10.4–14.7 months). Partial response was achieved in 7 of 23 patients, resulting in an overall response
of 30.4% (95% CI, 11.6–49.0). Following initiation of second-line chemotherapy, median PFS was 5.9 months (95% CI, 1–10.9 months)
and median OS was 12.5 months (95% CI, 3.5–21.5 months). The 1-year survival rate for all patients was 61.0% (95% CI, 29.5–82.0).
Adding these results to those of the 10 previously published trials, 75 of 326 patients, 23%, (95% CI, 18.7–27.3) presented
an overall response with the use of second-line platinum-based chemotherapy. The use of platinum combinations as second-line
chemotherapy seems to have a place in the management of patients with advanced NSCLC, especially those with an interval time
to progression greater than 6 months. 相似文献
7.
目的 探讨多西他赛联合替吉奥对比多西他赛单药二线冶疗晚期非小细胞肺癌的临床疗效.方法 收集经一线治疗后进展的晚期非小细胞肺癌患者100例,参照抽签法将患者随机分为试验组和对照组,每组各50例.试验组患者行多西他赛(60 mg/m2,静滴1 h,第1天)联合替吉奥(40 mg/m2,早晚饭后各服1次,连服14 d,每3周重复)治疗;对照组患者行多西他赛单药治疗(75 mg/m2,静滴1 h,第1天,每3周重复),所有患者随访至疾病进展或死亡.对比两组患者的临床疗效、生存情况及不良反应发生情况.结果 试验组患者的疾病控制率(72.00%)高于对照组患者(56.00%)(P﹤0.05);两组患者的客观缓解率比较,差异无统计学意义(P﹥0.05);试验组患者的中位无进展生存期为4.6个月(95%CI:3.994~5.206)长于对照组患者的3.1个月(95%CI:2.494~3.706)(P﹤0.05);试验组患者的中位生存期为9.2个月(95%CI:8.871~10.529)长于对照组患者的7.9个月(95%CI:5.575~10.225)(P﹤0.05);两组患者各种不良反应发生率及总不良反应发生率比较,差异均无统计学意义(P﹥0.05).结论 多西他赛联合替吉奥二线治疗晚期非小细胞肺癌的临床疗效优于多西他赛单药治疗. 相似文献
8.
Hirose T Shirai T Ishida H Ando K Sugiyama T Kusumoto S Hosaka T Nakashima M Ohmori T Adachi M 《Cancer chemotherapy and pharmacology》2007,60(2):267-274
We examined the safety and efficacy of the combination of docetaxel and irinotecan administered biweekly in patients with
refractory or relapsed advanced non-small cell lung cancer (NSCLC). Patients with previously treated NSCLC of stage III or
IV were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function.
From May 2003 through February 2006, 35 patients (27 men and 8 women; median age 64 years; age range 41–75 years) were enrolled.
Patients were treated every 4 weeks with docetaxel (33 mg/m2 on days 2 and 16) plus irinotecan (50 mg/m2 on days 1 and 15). None of the 35 patients achieved a complete response, but five achieved a partial response, for an overall
response rate of 14.3% (95% confidence interval, 4.8–30.3%). The median survival time was 8 months (range 2–29 months). The
median time to progression was 3 months (range 1–12 months). Grade 3 to 4 hematologic toxicities included leukopenia in 48.6%
of patients, neutropenia in 54.3%, and anemia in 25.7%. No patients had grade 3 to 4 diarrhea or nausea and vomiting. Although
one patient had grade 3 drug-induced interstitial pneumonia, all side effects were manageable, and there were no treatment-related
deaths. In conclusion, the combination of docetaxel and irinotecan administered biweekly is a safe and effective treatment
for refractory or relapsed NSCLC. However, the search for even more active regimens should be continued. 相似文献
9.
Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study 总被引:4,自引:0,他引:4
Manuel Constenla Ramon Garcia-Arroyo Isabel Lorenzo Nancy Carrete Begoña Campos Patricia Palacios 《Gastric cancer》2002,5(3):0142-0147
Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was
to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV).
Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status
0–2 were enrolled and received either 75 or 100 mg/m2 docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m2) plus LV (500 mg/m2), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two
cycles.
Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease.
The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months
(95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population.
The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed
in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients
reduced the incidence and severity of neutropenia. Other hematological toxicities were rare.
Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer.
This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer.
Received: December 25, 2001 / Accepted: April 22, 2002
Offprint requests to: M. Constenla 相似文献
10.
Feliu J Firvida JL Castro J Madroñal C Rodríguez-Jaráiz A Salgado M Belda-Iniesta C Casado E García-Mata J González-Barón M;Oncopaz Cooperative Group 《Cancer chemotherapy and pharmacology》2009,63(3):403-409
Purpose To determine the efficacy and safety of the combination therapy with docetaxel and cisplatin (CDDP) at low doses in elderly
patients with advanced NSCLC.
Patients and methods A total of 42 patients aged ≥70 years with previously untreated advanced NSCLC received docetaxel 75 mg/m2 plus CDDP 50 mg/m2 on day 1. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease
was detected.
Results By intent-to-treat analysis, the overall response rate was 31% (95% CI, 17.8–47.2%). A total of 18 patients (43%) had stable
disease and 11 (26%) progressed. Median time to progression was 5.2 months. Overall median survival was 8.9 months, with 1-year
actuarial survival rate of 41%. Eastern Cooperative Oncology Group performance status was improved in 18 patients (43%). The
chemotherapy regimen was well tolerated. A total of 11 patients (26%) had grade 3/4 adverse events: 7 (17%) neutropenia (one
of them was diagnosed with febrile neutropenia), 3 (7%) asthenia, 3 (7%) nausea/vomiting, 1 (2%) diarrhea, 1 (2%) thrombocytopenia
and 1 (2%) neurotoxicity. No death due to toxicity was seen.
Conclusion The combination of low-dose CDDP and docetaxel for elderly patients with advanced NSCLC is an efficient and well-tolerated
chemotherapeutic approach. 相似文献
11.
Lee JL Ryu MH Chang HM Kim TW Yook JH Oh ST Kim BS Kim M Chun YJ Lee JS Kang YK 《Cancer chemotherapy and pharmacology》2008,61(4):631-637
Purpose Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used as a first-line treatment of advanced
gastric cancer (AGC). Docetaxel has shown promising activity against this disease. In this study, we explored the efficacy
and safety of docetaxel monotherapy as salvage chemotherapy in AGC after F and P combination chemotherapy failed.
Materials and methods From October 2004 to October 2005, 49 eligible patients were enrolled in this study. The median treatment-free interval was
28.0 days, and 81.6% of patients had suffered cancer progression within 4 months after the withdrawal of first-line chemotherapy.
Docetaxel was given IV at a dose of 75 mg/m2 every 3 weeks, together with dexamethasone prophylaxis.
Results A total of 182 cycles of docetaxel were administered with a median of 3 (range 1–9) cycles. From an intention-to-treat analysis,
eight patients achieved objective response with a response rate of 16.3% (95% CI, 6.0–26.6). The median response duration
was 4.7 months. A total of 20 patients showed stable disease, but 17 patients suffered disease progression. At a median follow-up
duration of 11.3 months for surviving patients (range 6.3–18.8 months), the median time to disease progression was 2.5 months
(95% CI, 2.3–2.7) and the median overall survival time since the start of docetaxel monotherapy was 8.3 months (95% CI, 6.7–9.8).
Grade 3/4 neutropenia and febrile neutropenia occurred in 18.4% of patients and in 5.4% of cycles. The incidence of non-hematologic
toxicities of grade 3 or worse was asthenia 32.7%, diarrhea 10.2% and peripheral sensory neuropathy 8.2%.
Conclusion Docetaxel at 75 mg/m2 is active against AGC as second-line chemotherapy after prior exposure to F and P combination chemotherapy. The toxicity
profile is moderate. 相似文献
12.
Feliu J Martín G Castro J Sundlov A Rodriguez-Jaráiz A Casado E Lomas M Madroñal C Galán A Belda C Gonzalez-Barón M 《Cancer chemotherapy and pharmacology》2006,58(4):527-531
Purpose: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m2) followed by mitomycin C (8 mg/m2) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. Results: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3–4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6–21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. Conclusions: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate. 相似文献
13.
Pallis AG Christofillakis Ch Tselepatiotis E Agelaki S Vamvakas L Souglakos J Vardakis N Kalykaki A Kotsakis A Argiraki A Mavroudis D Georgoulias V 《Lung cancer (Amsterdam, Netherlands)》2007,55(1):101-107
PURPOSE: To evaluate the activity and toxicity of the sequential administration of docetaxel followed by gefitinib in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Forty-one patients pre-treated with at least one prior chemotherapy regimen (platinum- or taxane-based) for advanced/metastatic NSCLC received three cycles of docetaxel 30 mg/m2, administered as a 1-h IV infusion, on days 1, 8 and 15 of each 4-week cycle followed by gefitinib 250 mg daily po. Gefitinib treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of patients consent. RESULTS: Two (4.9%) patients achieved a partial response and 10 (24.4%) stable disease, for a disease control rate of 29.3% (95% CI: 15.3%-43.2%) while on weekly docetaxel treatment. Additionally, progressive disease (PD) was observed in 29 (70.7%). No objective responses were observed during the gefitinib maintenance therapy; however, 17 (41.5%) patients presented stable disease maintained for more than 2 months. Median time to progression was 3.0 months (range: 1-38.3 months; 95% CI: 2.4-3.6); median overall survival 6.9 months (range: 1.2-40.2 months; 95% CI: 5.34-8.52) while the 1-year survival was 28.8%. Therapy was generally well tolerated with diarrhea and rash being the most frequent toxicities. CONCLUSIONS: The sequential administration of docetaxel and gefitinib was well tolerated and moderately active against advanced pre-treated NSCLC. 相似文献
14.
C Kosmas N Tsavaris M Vadiaka N Stavroyianni A Koutras N Malamos A Onyenadum S Rokana A Polyzos H P Kalofonos 《Cancer》2001,92(11):2902-2910
BACKGROUND: Treatment options for patients with recurrent nonsmall cell lung carcinoma (NSCLC) remain limited as a result of poor activity of older agents after platinum-based therapy. In the current Phase II study, the authors evaluated the combination of gemcitabine and docetaxel in patients with recurrent NSCLC. METHODS: Patients with advanced NSCLC (Stage IIIB-IV), a World Health Organization performance status (PS) < or = 2, prior paclitaxel plus platinum-based chemotherapy, and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered as follows: gemcitabine 1000 mg/m(2) was administered on Days 1 and 8 followed by docetaxel 100 mg/m(2) on Day 8, and this regimen was recycled every 21 days. Prophylactic granulocyte-colony stimulating factor was administered on Days 10-14 or until the patient achieved a white blood cell count > or = 5000/microL. RESULTS: Of 43 patients who were entered on the study, 41 patients were evaluable for response, and all were evaluable for toxicity. The median patient age was 63 years (range, 47-70 years), the median PS was 1 (range, 0-2), there were 38 male patients, and there were 5 female patients. Four patients had Stage IIIA disease, 17 patients had Stage IIIB disease, and 22 patients had Stage IV disease. Histologies included 19 patients with adenocarcinoma, 18 patients with squamous cell carcinoma, and 3 patients with large cell carcinoma. Metastatic sites included lymph nodes in 28 patients, bone in 6 patients, liver in 5 patients, brain in 5 patients, lung nodules in 8 patients, adrenals in 7 patients, and other sites in 3 patients. All patients had received prior paclitaxel plus platinum-based treatment; 28 patients had received prior paclitaxel, ifosfamide, and cisplatin. Objective responses were partial response (PR) in 14 of 43 patients [33%; 95% confidence interval [95%CI], 18.5-46.6%], stable disease (SD) in 16 of 43 patients (37%; 95% CI, 22.8-51.6%), and progressive disease (PD) in 13 of 43 patients (30%; 95% CI, 16.3-43.7%). The median time to disease progression was 6 months (range, 1.0-20.0+ months), and the median survival was 8.5 months (range, 1.5-20.0+ months). The 1-year survival rate was 28%. Grade 3-4 neutropenia was experienced by 53% of patients (30% Grade 4), with 14% of patients experiencing febrile neutropenia. Grade 3 thrombocytopenia was experienced by 7% of patients (no Grade 4), whereas other Grade 3 nonhematologic toxicities were never encountered. CONCLUSIONS: The combination of gemcitabine and docetaxel is active and is well tolerated in patients with advanced NSCLC who have failed prior taxane plus platinum chemotherapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of patients with recurrent NSCLC. 相似文献
15.
Manuel Cobo-Dols Silvia Gil-Calle Esther Villar-Chamorro Inmaculada Alés-Díaz Francisco Carabantes-Ocón Julia Alcalde-García Vanesa Gutiérrez-Calderón Álvaro Montesa-Pino Juan J. Bretón-García Manuel Benavides-Orgaz 《Clinical & translational oncology》2006,8(7):519-524
Backbround In this Phase I/II trial, the maximum-tolerated dose (MTD) and activity of cisplatin plus vinorelbine (VRL) administered in
continuous in-fusion as first-line treatment of advanced non small cell lung cancer (NSCLC) was determined in 12 consecutive
chemotherapy-naive patients with advanced NSCLC.
Patients and methods The dose of cisplatin was 100 mg/m2 in all patients, and vinorelbine was administered as an initial intravenous (iv) bolus of 8 mg/m2 on day 1 followed by a 4-day continuous iv infusion at 4 different 24 h dose levels (DLs) to be repeated every 21 days. All
12 patients (47 cycles) were evaluable for response and toxicity.
Results The MTD was 8 mg/m2 bolus followed by a continuous iv infusion of 8 mg/m2 per day over 4 days. The dose limiting toxicities (DLT) were febrile neutropenia in 4 patients and grade 3 mucositis in 1
patient. There was less neuro-toxicity and compared to the weekly bolus scheme. There was no significant cumulative toxicity
after 3 cycles. Partial responses were observed in 6 patients; an overall response rate of 50% (95% CI: 30–65%). Median time
to progression was 5,5 months (95% CI: 1,5–11 months) and median survival was 11 months (95% CI: 5–20 months).
Conclusions The results demonstrate that, in this setting of first-line treatment of NSCLC, cisplatin plus vinorelbine at 8 mg/m2 bolus followed by a continuous infusion of 8 mg/m2 per day over 4 days is the recommended schedule. Further trials would be useful to establish activity of this combination. 相似文献
16.
Kyoung Ha Kim Young Suk Park Myung Hee Chang Hyo Song Kim Hyun Jung Jun Jieun Uhm Seong Yoon Yi Do Hyoung Lim Sang Hoon Ji Min Jae Park Jeeyun Lee Se Hoon Park Joon Oh Park Ho Yeong Lim Won Ki Kang 《Cancer chemotherapy and pharmacology》2009,64(2):347-353
Purpose We designed this phase I/II study of docetaxel–oxaliplatin combination chemotherapy to determine the dose-limiting toxicity
(DLT), maximum tolerated dose and efficacy as a first-line treatment in patients with advanced gastric cancer.
Methods Patients with histologically proven, chemo-naive gastric adenocarcinoma were eligible. For the phase I part, three dose levels
of oxaliplatin and docetaxel every 3 weeks were tested in a cohort of three patients for each level (respectively, 100 and
60 mg/m2, 100 and 75 mg/m2, 130 and 75 mg/m2). Patients were treated up to a maximum of nine cycles of oxaliplatin and docetaxel unless there was documented disease progression,
an unacceptable adverse event, or withdrawal of consent.
Results No DLT was observed at any of the three levels tested in the phase I portion. Therefore, oxaliplatin 130 mg/m2 and docetaxel 75 mg/m2 were recommended for the phase II study. All 47 patients were evaluable for toxicity and treatment response. The overall
response rate was 55.3% (95% CI, 40.6–70.1%) and median duration of response was 4.2 months (range 0.9–9.5 months). After
a median follow-up duration of 13.3 months, median overall survival was 12.7 months (95% CI: 10.4–14.9). The median time to
progression was 5.0 months (95% CI, 3.4–6.5 months). The main toxicities (grade 3 or 4) were febrile neutropenia (14.9%),
neutropenia (23.4%), diarrhea (10.6%) and neurotoxicity (8.5%).
Conclusion The combination of docetaxel and oxaliplatin was feasible with favorable toxicity profile and showed a promising anti-tumor
activity in unresectable, metastatic gastric cancer patients. 相似文献
17.
Paolo Piacentini Emilia Durante Annarita Trolese Anna Mercanti Andrea Bonetti 《Gastric cancer》2012,15(1):106-110
Abstract
The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991–7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m2 and cisplatin 25 mg/m2 on day 1, followed by 5-FU 180 mg/m2/day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week’s rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40–78 years). The median number of cycles per patient was 4 (range 2–6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16–51], a median time to progression of 6.4 months (95% CI 5.4–7.4), and a median overall survival of 10.7 months (95% CI 6.6–14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III–IV toxicities observed in >5% of patients were anemia and mucositis. 相似文献18.
Mark Clemons Anil A. Joy Radhi Abdulnabi Mauricio Kotliar Jodi Lynch Johan P. Jordaan Neill Iscoe Karen Gelmon 《Breast cancer research and treatment》2010,124(1):177-186
Capecitabine is frequently used in the treatment of recurrent/progressive metastatic breast cancer (MBC) after prior anthracycline
and taxane therapy. With the intention of improving the efficacy of single agent capecitabine, we initiated a randomized,
double-blind, placebo-controlled Phase II study of the novel serine/threonine kinase inhibitor enzastaurin in combination
with capecitabine in a heavily pretreated patient population. Patients received capecitabine 1,250 mg/m2 twice daily plus enzastaurin 500 mg/day, or capecitabine plus placebo. The capecitabine was administered for the first 14 days
of each 21 day cycle. The primary outcome was progression-free survival (PFS) using the log-rank test (1-sided significance
level of 0.20). Of 109 patients assessed for eligibility, 85 were enrolled, randomized, and treated (42 and 43 patients in
each respective treatment group). The study was terminated early following a preplanned futility analysis. Median PFS (95%
CI) was 2.8 (2.1–4.6) months with capecitabine plus enzastaurin versus 4.3 (2.9–6.2) months with capecitabine plus placebo
(adjusted hazard ratio: 1.728 [1.00–2.97]; P = 0.048). Median overall survival (95% CI) was lower with capecitabine plus enzastaurin than with capecitabine plus placebo
(9.9 [7.0–16.6] months vs 14.9 [9.9–19.3] months, P = 0.181). Grade 3/4 adverse events were more frequent with capecitabine plus enzastaurin (42.9% vs 32.6%). Given the lack
of PFS benefit, capecitabine plus enzastaurin is unsuitable as therapy for patients with recurrent/progressive MBC after prior
anthracycline and taxane therapy. This trial is registered on (identifier: NCT00437294). 相似文献
19.
Carlson RW O'Neill A Vidaurre T Gomez HL Badve SS Sledge GW 《Breast cancer research and treatment》2012,133(3):1049-1056
EGFR signalling pathways appear involved in endocrine therapy resistance in breast cancer. This trial estimates the antitumor efficacy and toxicity of the EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects with estrogen receptor and/or PgR positive, metastatic breast cancer were randomized into this phase II study of gefitinib (initial dose was 500 mg orally daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks. The primary endpoint was clinical benefit (complete responses plus partial responses plus stable disease for 6 months or longer). 141 eligible subjects were enrolled, 72 in the anastrozole plus gefitinib arm, and 69 in the fulvestrant plus gefitinib arm. Anastrozole plus gefitinib had a clinical benefit rate of 44% [95% confidence interval (CI) 33-57%] and fulvestrant plus gefitinib 41% (95% CI 29-53%). Median progression-free survival was 5.3 months (95% CI 3.1-10.4) versus 5.2 months (95% CI 2.9-8.2) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. Median survival was 30.3 months (95% CI 21.2-38.9+) versus 23.9 months (95% CI 15.4-33.5) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. In general, the toxicity is greater than expected for single agent endocrine therapy alone. Anastrozole plus gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in the treatment of estrogen and/or PgR positive metastatic breast cancer, and the rates of response are not clearly superior to gefitinib or endocrine therapy alone. Further studies of EGFR inhibition plus endocrine therapy do not appear warranted, but if performed should include attempts to identify biomarkers predictive of antitumor activity. 相似文献
20.
Niho S Kubota K Goto K Ohmatsu H Matsumoto T Kakinuma R Nishiwaki Y 《Cancer chemotherapy and pharmacology》2003,52(1):19-24
PURPOSE: In a randomized trial, docetaxel monotherapy yielded longer survival than the best supportive care in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy, and combination chemotherapy regimens containing docetaxel have been assessed to enhance the efficacy of second-line chemotherapy. We conducted a phase I/II trial of gemcitabine and docetaxel in patients with recurrent NSCLC after platinum-based chemotherapy and with an ECOG performance status (PS) of 0 or 1. PATIENTS AND METHODS: Docetaxel administration was fixed at a dosage of 60 mg/m(2) on day 8, and gemcitabine was administered on days 1 and 8. The starting dose level of gemcitabine was 800 mg/m(2) (level 0), and the subsequent dose level of gemcitabine was 1000 mg/m(2) (level +1). Treatment was repeated every 3 weeks. RESULTS: In the phase I study, 13 patients were enrolled, and in the phase II study, 29 patients were enrolled. Neutropenic fever and omission of treatment on day 8 due to leukopenia (leukocyte count less than 3000/mm(3)) were dose-limiting toxicities (DLTs). Three of six patients experienced DLTs at level +1, which was the maximum tolerated dose. Gemcitabine 800 mg/m(2) on days 1 and 8 plus docetaxel 60 mg/m(2) on day 8 (level 0) was recommended for the phase II study. An objective response was observed in 8 (28%) of the 29 patients. The median time to disease progression was 4.2 months (95% CI 0.9-7.7 months). The median survival time was 11.1 months (95% CI 9.9-12.4 months), and the 1-year survival rate was 41%. The most common toxicity, though mild, was hematologic, and consisted of grade 4 neutropenia (18%), grade 3 febrile neutropenia (11%), and grade 3 thrombocytopenia (11%). There were no toxic deaths. Grade 3 non-hematologic toxicities included nausea (4%) and rash (4%). CONCLUSIONS: The combination chemotherapy of gemcitabine and docetaxel is active and well tolerated in patients with recurrent NSCLC after platinum-based chemotherapy and with a good PS. 相似文献