A phase II study of sequential docetaxel and gemcitabine followed by docetaxel and carboplatin as first-line therapy for non-small cell lung cancer

Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for inoperable NSCLC. Twenty-six chemo-naïve patients aged less than 75 years with histologically or cytologically confirmed unresectable stage IIIB, IV or relapsed post-operative metastatic NSCLC were included in the study. Gemcitabine 1,250 mg/m² was administered and was followed by docetaxel 65 mg/m². Treatment was administered on days 1 and 14 in a 28-day cycle for three consecutive cycles. If patients had no progressive disease after three cycles of chemotherapy, they received another three cycles of docetaxel 65 mg/m² followed by carboplatin AUC5 on day 1 in a 21-day cycle. Recombinant human granocyte colony-stimulating factor (rhG-CSF) was given prophylactically. In addition, all patients received standard pre- and post- treatment with oral dexamethasone. Response rates at three cycles were: 19% achieved a partial response (PR), 46% had stable disease (SD) and 23% had progressive disease. At six cycles, 8% of the patients maintained PR, 19% showed SD and 35% had progressive disease. The median time-to-disease progression was 6 months. The median survival time of patients was 10 months while, at the end of the first year, the patients who managed to get through the complete therapy (20 patients) had a survival rate of 38%. This detailed analysis of 20 patients showed that 80% of the patients survived for up to 6 months, 38% up to 12 months and 19% for more than a year. The only risk factor associated with the hazard of death among the factors studied was the performance status of the patients. Patients with PS = 0 presented a median survival time of 13 months and those with PS = 1, it was only 9 months. Non-haematological and haematological toxic effects were generally mild to moderate and entirely manageable.     

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study

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.     

Phase II study of weekly carboplatin and irinotecan as first-line chemotherapy for patients with advanced non-small cell lung cancer

Purpose

Platinum-based doublet chemotherapy has a major role in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The weekly fractionated administration of cisplatin for patients with NSCLC has been shown to be active. Irinotecan and carboplatin are effective against NSCLC and demonstrated synergism with non-cross-resistance in preclinical studies. We conducted a phase II study of weekly combination of carboplatin and irinotecan as first-line chemotherapy for patients with advanced NSCLC.

Methods

From March 2009 to November 2011, 24 patients who were diagnosed with inoperable or metastatic NSCLC were enrolled. Treatment consisted of carboplatin at an AUC 2.5 mg/mL/min over 30-min intravenous infusion and irinotecan 65 mg/m² over 90-min intravenous infusion on day 1 and day 8, respectively. The treatment was repeated every 3 weeks.

Results

One patient (4.2 %) achieved complete response, and seven (29.2 %) showed partial response. Overall response rate was 33.3 %, with median response duration of 4.55 months. Nine patients had stable disease, and disease control rate was 70.8 %. With median follow-up of 12.8 months, median progression-free survival was 4.5 months (95 % CI 1.8–7.2), and median overall survival was 15.5 months (95 % CI 6.9–24.1). Major toxicity was myelosuppression. Grade 3–4 neutropenia and thrombocytopenia occurred in 50 and 20.8 % of patients, respectively. Two patients experienced febrile neutropenia. Non-hematologic toxicities were generally mild. One patient suffered grade 4 diarrhea, and one treatment-related death due to pneumonia was occurred.

Conclusion

The weekly combination of carboplatin and irinotecan showed favorable activity and manageable toxicity profiles in chemo-naïve patients with advanced NSCLC. Our results suggest that this regimen can be a reasonable chemotherapeutic option for patients with advanced NSCLC.     

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.     

Phase II study of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer

Purpose

This phase II study is performed to evaluate the safety, efficacy and tolerability of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer (NSCLC).

Patients and methods

All patients were treated with the combination of docetaxel 35 mg/m² by IV infusion over 30–60 min weekly, on days 1, 8, and 15, for 3 weeks followed by 1 week of rest, with intravenous carboplatin (AUC 6) administered immediately afterward on day 1. Cycles were repeated every 28 days.

Results

Forty-seven (95.9%) of the 49 patients were assessable for response, one case of complete response and 17 cases of partial response were confirmed, giving an overall response rate of 36.7% (95% CI 23.2–50.2%). The median time to progression and overall survival (OS) for all patients were 5.2 months (95% CI 4.1–6.3 months) and 10.4 months (95% CI 7.3–13.5 months), respectively. The estimate of OS at 12 months was 37.6% (95% CI 24.0–51.2%). The most severe hematologic adverse event was anemia, which occurred with grade 3/4 intensity in 7 (14.9%) patients. Neutropenia occurred with grade 3 intensity in 4 (8.5%) patients. However, no grade 4 neutropenia was observed. Grade 3 nausea/vomiting, diarrhea, asthenia, nail changes, and skin reaction were observed in 6 (12.8%), 3 (6.4%), 2 (4.3%), 2 (4.3%) and 1 (2.1%) patients. Yet, no grade 4 non-hematologic toxicity was observed.

Conclusions

The combination of carboplatin with weekly docetaxel is a tolerated treatment modality with encouraging activity and survival outcome in previously untreated patients with advanced NSCLC.     

Phase II trial of weekly docetaxel and gemcitabine as first-line therapy for patients with advanced non-small cell lung cancer

Background A platinum doublet has been the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) and good performance status. This treatment results in almost a doubling of 1-yr survival, along with an improvement in quality of life despite treatment-related toxicities. However, platinum-based treatment may be associated with significant toxicity. Materials and Methods In this trial, we prospectively evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC. The endpoints of this study included objective response rate, survival, and toxicity. Forty-two patients with previously untreated, advanced NSCLC with PS 0-1 were included. Patients received docetaxel (36 mg/m²) and gemcitabine (600 mg/m²) on d 1, 8, and 15 of a 28-d cycle. Responses were assessed every two cycles. The median age was 63 yr; with 22 males and 20 females; 67% were ≥60 years old; and 38 patients had stage IV disease. Results In the intent-to-treat (ITT) analysis of response, 16 patients had a partial response (38%) and 15 patients had stable disease (36%). The 1-yr survival was 48%; median survival for all patients was 11.3 mo and the median progression-free survival was 5.1 mo. Toxicities (≥grade 3) included neutropenia (29%), asthenia (26%), diarrhea (14%), thrombocytopenia (10%), pneumonitis (7%), peripheral neuropathy (5%), peripheral edema (5%), nail changes (2%), and myositis (2%). Conclusions This study demonstrated that this non-platinum doublet (docetaxel+gemcitabine) given on a weekly schedule for advanced NSCLC was well tolerated with efficacy comparable to that reported with platinum-based chemotherapy regimens.     

Phase II tailored S-1 regimen study of first-line chemotherapy in elderly patients with advanced and recurrent non-small cell lung cancer

Purpose

We investigated the efficacy and toxicity of a novel oral 5-fluorouracil (5-FU) formulation (S-1), administered according to a tailored dose regimen.

Methods

S-1 was administered orally for 28?days, followed by 14?days of no treatment, in 23 patients who received a tailored dose of S-1, adjusted on the basis of individual creatinine clearance and body surface area. In 8 of the patients, pharmacokinetic study was performed on the 6 points on 7th day after S-1 administration.

Results

Of the 23 patients enrolled in this study, 2 (8.7?%) had a partial response and 14 (60.9?%) had stable disease. The disease control rate was 69.6?% (16/23) (95?% confidence interval, 50.8?C88.4?%). Grade 3/4 hematologic and non-hematologic toxicities were minor. In the pharmacokinetic study group, the maximum plasma concentration (C _max) and the area under the plasma concentration curve of 5-FU at all 6 points after administration of the tailored S-1 dose regimen were similar to the values reported in a previous study describing cancer patients with normal renal function who received a standard dose of S-1 (80?mg/m²/day).

Conclusions

Our results suggest that tailored S-1 monotherapy is safe and therapeutically useful as first-line treatment for elderly patients with advanced and recurrent non-small cell lung cancer.     

多西他赛联合顺铂一线治疗晚期非小细胞肺癌的临床观察

目的观察多西他赛联合顺铂一线治疗晚期非小细胞肺癌的疗效和不良反应。方法67例晚期非小细胞肺癌患者入组。多西他赛75mg/m^2,d1,顺铂25mg/m^2,d1～3。21d为一个周期。观察临床缓解率、1年生存率和中位生存期。结果该方案的客观有效率为43.8%（28/64）,毒副反应主要为恶心、呕吐和骨髓抑制,mTTP为5.4个月,1年生存率为45.3%（29/64）,中位生存期为11.2个月。结论多西他赛联合顺铂一线治疗晚期NSCLC更能体现其价值。     

Phase II study with fractionated schedule of docetaxel and cisplatin in patients with advanced non-small cell lung cancer

Background

Docetaxel and cisplatin combination chemotherapy is established first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). We evaluated a weekly schedule of docetaxel and cisplatin for efficacy and tolerability in patients with chemotherapy-naive NSCLC.

Methods

Patients enrolled in this study had stage IIIB or IV NSCLC with measurable disease, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Treatment consisted of docetaxel 40 mg/m² and cisplatin 35 mg/m² given on D1 and D8 every 3 weeks. Patients were evaluated for response after every 2 cycles of treatment.

Results

Thirty six patients were enrolled, and 35 underwent treatment. Of these, 29 were males and 7 females, median age was 61 years (range, 38–68). About 31 patients had ECOG PS 0-1 and 4 patients had ECOG PS 2. Fifty seven percentage (20/35) of patients had adenocarcinoma and 74.3% (26/35) had stage IV disease. A total of 153 cycles of chemotherapy were administered. Of the 35 patients treated, 17 (48.6%) achieved partial response, 11 (31.4%) showed stable disease, and 6 (17.1%) had progressive disease. Median duration of response was 5.3 months (95% CI: 4.2–6.2 months), and median time to disease progression was 4.6 months (95% CI: 2.9–6.3 months). Estimated overall survival at 1 year was 65.7%. The major hematologic toxicity was myelosuppression. Grade 3 or 4 anemia occurred in 6 cycles, and grade 3 or 4 neutropenia was observed in four cycles. Major non-hematologic toxicities were grade 3 nausea in three patients and grade 3 fatigue in two patients. Three patients developed pneumonia and one patient had infectious colitis. There were no treatment-related deaths in this study.

Conclusions

Weekly schedule of docetaxel and cisplatin as first-line treatment for NSCLC had good efficacy and manageable toxicity.     

Cisplatin and weekly docetaxel as first-line therapy in patients with advanced non-small cell lung cancer a phase II study

BACKGROUND: Based on the results of previous phase I studies, in the current phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The eligibility criteria for the study included newly diagnosed stage IIIB/IV NSCLC, age < or = 75 years, Eastern Cooperative Oncology Group performance status of 0-2, adequate organ functions, and signed informed consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m2 on day 1, and docetaxel, 25 mg/m2 on days 1, 8 and 15 every 4 weeks. RESULTS: Between January 2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable patients. The median time to progression was 6.4 months (range, 2.5-26.3) and median overall survival was 10.01 months (range, 5-28.3). The regimen was well tolerated with no grade 4 toxicity. CONCLUSIONS: Cisplatin plus weekly docetaxel is an effective and well-tolerated regimen in chemo-naive patients with advanced NSCLC. A phase III study of weekly versus the conventional regimen of every three weeks should be conducted to compare the survival benefits, toxicity profile and quality of life.     

Phase II study of carboplatin-paclitaxel combination chemotherapy in elderly patients with advanced non-small cell lung cancer

BACKGROUND: More than 30% of cases of non-small cell lung cancer (NSCLC) arise in patients aged > or =70 years. The efficacy and safety of carboplatin-paclitaxel combination chemotherapy in elderly patients with advanced NSCLC were evaluated in a phase II trial. METHODS: Twenty-five patients aged > or =70 years (median, 76; range, 70-83) with chemotherapy-naive advanced NSCLC were enrolled between January 2001 and July 2003. Additional criteria included the presence of measurable lesions, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients received carboplatin at an area under the curve of 5 mg/ml/min and paclitaxel at 180 mg/m(2) on the first day of consecutive 3 week periods. RESULTS: The patients included four with stage IIIB, 19 with stage IV and two with recurrent disease. The median number of treatment cycles was three (range, 1-4). One complete response and six partial responses, yielding an objective response rate of 28%, were obtained. The median survival time was 12.3 months and the 1-year survival rate was 52%. Hematological toxicities of grade 3 or 4 included leukopenia (40%), neutropenia (68%) and anemia (4%). Non-hematological toxicities of grade 3 included arthralgia-myalgia (16%) and neuropathy (12%). The objective response rate for patients aged > or =75 years (n = 15) was 26%, and no evidence of excessive toxicity in these patients was apparent compared with those aged <75 years. CONCLUSION: The combination carboplatin-paclitaxel at these doses is a feasible treatment option with a favorable toxicity profile for fit elderly patients with advanced NSCLC.     

A phase II study of docetaxel and vinorelbine combination chemotherapy in patients with advanced non-small cell lung cancer

A phase II study was conducted to determine the efficacy and the safety of docetaxel combined with vinorelbine as first-line chemotherapy in patients with metastatic or unresectable non-small cell lung cancer (NSCLC). 39 patients, median age 54 years (range: 35-69), with stage IIIB (5 patients; 13%) or IV (34 patients; 87%) NSCLC were treated with 75 mg/m(2) docetaxel given intravenously (i. v.) over 1 h on day 1 and with 20 mg/m(2) vinorelbine given i.v. over 15 to 30 min on days 1 and 5. Cycles were repeated every 3 weeks. 9 of the 39 patients had a partial response (overall response rate 23.1%, 95% confidence interval (CI): 11.1-39.3%) with a median duration of response of 20 weeks (95% CI; 17-30). The median survival was 40 weeks (95% CI: 21-49 weeks) with a 1-year survival rate of 31% in the intent-to-treat population. Neutropenia grade IV occurred in 33 patients (92%). 16 patients (41%) experienced febrile neutropenia with a concomitant stomatitis in 9 patients (23%). One patient died due to febrile neutropenia associated with a grade 4 stomatitis and 1 patient due to a septicaemia concomitant with a grade 4 neutropenia. Although the combination of docetaxel and vinorelbine is feasible, the efficacy does not seem to be improved compared with single-agent docetaxel or vinorelbine and the rate of febrile neutropenia is unacceptable in this population with incurable disease. Therefore, different doses and/or schedules are to be explored.     

Phase II study of sequential administration of docetaxel followed by doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel). RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months). CONCLUSION: This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.     

Phase II study of sequential chemotherapy with docetaxel-estramustine followed by mitoxantrone-prednisone in patients with advanced hormone-refractory prostate cancer

Sequential chemotherapy may improve treatment efficacy avoiding the additive toxicity associated with concomitant polichemotherapy in hormone-refractory prostate cancer (HRPC). Forty patients received docetaxel 30 mg m(-2) intravenous (i.v.), weekly, plus estramustine 280 mg twice daily for 12 weeks. After 2 weeks rest, patients with a decline or stable PSA were treated with mitoxantrone 12 mg m(-2) i.v. every 3 weeks plus prednisone 5 mg twice daily for 12 cycles. Forty patients were assessable for toxicity after docetaxel/estramustine. Main toxicities were grade 3-4 AST/ALT or bilirubin increase in seven patients (17.5%) and deep venous thrombosis (DVT) in four patients (10%). Twenty-seven patients received mitoxantrone/prednisone. Main toxicities included DVT in one patient (3.7%) and congestive heart failure in two patients (7%). Thirty-nine patients were assessable for PSA response. Twenty-nine patients (72.5%; 95% CI 63-82%) obtained a >/=50% PSA decline with 15 patients (37.5%; 95% CI 20-50%) that demonstrated a >/=90% decrease. Median progression-free and overall survival were respectively 7.0 (95% CI 5.8-8.2 months) and 19.2 months (95% CI 13.9-24.3 months). In conclusion, although this regimen demonstrated a favourable toxicity profile, sequential administration of mitoxantrone is not able to improve docetaxel activity in patients with HRPC.     

Phase II study of alternating chemotherapy regimens for advanced non-small cell lung cancer

PURPOSE: We assessed the use of alternating drugs with differing mechanisms of action as treatment for advanced non-small cell lung cancer. BACKGROUND: We hypothesized that the shape of a dose-response curve would be determined by the major mechanisms of resistance of a cancer to the drug being studied. Assessment of data from published clinical trials suggested that if our hypothesis were correct resistance of non-small cell lung cancer to most agents is due to "saturable passive" resistance mechanisms (non-competitive inhibition of drug effect due to deficiency of a factor required for drug effect) rather than to "active" resistance mechanisms (competitive inhibition of drug effect due to excess of a factor) or to "non-saturable passive resistance (due to factor alteration or mutation). Using drugs with differing mechanisms of action is a strategy that might be of value against passive resistance. METHOD: In patients with advanced non-small cell lung cancer, we used four alternating cisplatin-based regimens. In each regimen, cisplatin 80 mg/m(2) was given iv on day 1 of each course. The regimens were: cisplatin + vinorelbine 25 mg/m(2) days 1, 8 and 15, cisplatin + gemcitabine 1000 mg/m(2) days 1, 8 and 15, cisplatin + paclitaxel 200 mg/m(2) day 1 iv over 1h, and cisplatin + etoposide 100 mg/m(2) po days 1-6. Patients were assigned randomly to different regimen sequences. Patients first received 1 course of each of these 4 regimens, then received 1 further course of each of single agent vinorelbine, gemcitabine, paclitaxel and etoposide (at the same doses as in courses 1-4), without cisplatin. (Cisplatin was omitted from courses 5-8 to limit cumulative toxicity.) Change in tumor size was measured after each course. RESULTS: Thirty-six patients were entered. One patient achieved complete remission and nine achieved partial remissions, for an objective response rate of 28% (95% confidence intervals, 13-43%). Nineteen patients (53%) (95% confidence intervals, 37-69%) had stable disease. Eleven patients had growth of >10% on one regimen followed by tumor shrinkage of >10% on a later one. Median survival was 8.1 months, 1-year survival was 28% and 2-year survival was 6%. No unexpected toxicity was seen. CONCLUSIONS: The use of four alternating regimens is feasible in advanced non-small cell lung cancer. Response rates and survival times were comparable to those observed for standard chemotherapy approaches, suggesting that this strategy does not offer any major advantage. We plan to explore the hypothesis that this approach failed since tumor cells surviving first exposure to chemotherapy rapidly down-regulate their ability to undergo apoptosis.     

多西他赛单药一线治疗老年晚期非小细胞肺癌的临床观察

目的:观察多西他赛单药一线治疗老年晚期非小细胞肺癌(NSCLC)的疗效、临床受益反应(CBR)及不良反应.方法:24例经病理学或细胞学确诊的老年晚期NSCLC患者(≥60岁),应用多西他赛30-37.5mg/m2,静脉滴注,第1、8天给药,每21天为1周期;对照组31例给予最佳支持治疗(BSC).结果:多西他赛治疗组有效率(RR)为25.0%,中位缓解时间为6.5个月,中位肿瘤进展时间(TTP)为5.6个月,中位生存期(OS)为11.4个月,1年生存率为38.2%;对照组有效率(RR)为0%,TTP为2.3个月,OS为4.8个月,1年生存率为9.7%.治疗组临床受益反应较对照组明显提高(P<0.01).治疗组药物不良反应较轻,无因不良反应需停药者.结论:多西他赛单药一线治疗老年晚期NSCLC疗效明确,不良反应较轻,耐受性较好.     

Phase II study of docetaxel in the treatment of patients with advanced non-small cell lung cancer in routine daily practice

The purpose of this study was to evaluate the efficacy and safety of docetaxel as first- and second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) under routine clinical conditions. Two hundred and three patients with advanced NSCLC received docetaxel 100 mg/m2 (1-h intravenous infusion) every 3 weeks, with oral corticosteroid pre-medication, of whom 173 were eligible. Median age was 60 (29-78) years and median Karnofsky performance status was 80% (60-100). A total of 77% of patients had metastatic disease, 33% had bone metastases and 18% had liver metastases. The treatment was second-line or more for 72 patients (35%). Overall response rates in the eligible population were 19.7% [95% CI, 12.5-23.0] for both treatments, 22.6% for first-line treatment and 13.8% for second-line treatment. Median survival was 8.3 months and 1-year survival was 35% for the overall population (8.7 months and 38%, respectively, for patients receiving first-line treatment and 7.2 months and 27%, respectively, for patients receiving second-line treatment). Neutropenia, grade 3 and 4, occurred in 57% of the cycles and 5% of patients experienced febrile neutropenia. Alopecia (62% of patients), neuro-sensory symptoms (32%), asthenia (28%), diarrhea (22%), nausea (22%) and nail disorders (20%) were the most common non-hematological adverse effects. A total of 33% of patients suffered fluid retention, despite the use of corticosteroid pre-medication, but this was only severe in 1.5% of patients. It was possible to confirm the efficacy of docetaxel as a single agent for first- and second-line chemotherapy in a large patient population treated in a community setting.     

Gemcitabine and vinorelbine followed by weekly docetaxel in patients with advanced non-small-cell lung cancer: a phase II trial of sequential chemotherapy

Objective We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Eligibility criteria: stage IV NSCLC, Performance status ≤2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m² plus gemcitabine 1000 mg/m², on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m² weekly until progression or unacceptable toxicity. Results 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2–6). Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3–16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6–25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease.     

Phase II non-randomized study of three different sequences of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer

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.