A phase II study of weekly paclitaxel and carboplatin in previously untreated patients with advanced non-small-cell lung cancer

Purpose: Both paclitaxel (P) and carboplatin (C) have a significant activity in non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose intense, and has a favorable toxicity profile. To evaluate the efficacy and toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II study in patients with advanced NSCLC (III B with pleural effusion and stage IV). Patients and Methods: Eligible patients were treated with paclitaxel 100 mg/m² intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This treatment was administered weekly for 3 of every 4 wk until disease progression or intolerable toxicities. Results: Of the 30 patients enrolled in the study, one patient did not meet the eligibility criteria. Of the remaining 29 patients, 6 did not complete at least two cycles of treatment and hence were not assessable for response. The overall response rate was 43.5% (10/23) (all partial responses). An additional 43.5% had stable disease. The median time to progression was 162 d and the median duration of response was 169 d. Overall survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8 mo. We observed the following grade 3/4 toxicities: hypersensitivity to paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%), thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced grade 2 neuropathy. Conclusions: We conclude that weekly paclitaxel and carboplatin is active and very well tolerated in patients with advanced NSCLC.     

Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: A phase II study

Background: Based on the high activity of single-agent paclitaxel and thesuperior one-year survival rates of patients with non-small-cell lung cancer(NSCLC) treated with carboplatin, a phase II trial was initiated using bothagents in patients with inoperable stages III and IV disease to investigatethe efficacy and toxicity of the combination.Patients and methods: Since July 1995, 60 patients fulfilling alleligibility criteria entered this study. All patients received paclitaxel 175mg/m² as a three-hour infusion, and carboplatin dosed to anarea under the concentration-time curve of seven, every three weeks. Nogranulocyte colony-stimulating factor was given. Of the 56 male and fourfemale patients, the median age was 57 years (range 29 to 75 years) and themedian Eastern Co-Operative Oncology Group performance status was one. Mostof the patients had stage IV (34) adenocarcinoma (31) with low differentiation(28). The median number of chemotherapy cycles was three, with a range of oneto eight.Results: Of 55 evaluable patients, 15 (27.3%) achieved partialresponses, 15 (27.3%) had stable disease, and 25 (45.4%) hadprogressive disease. The median survival was 8.95 months and 21.6% ofthe patients survived more than one year. Grade 2/3 nonhematologic toxicityincluded alopecia (59%), neurotoxicity (3%), andmyalgia/arthralgia (10%). Grade 2/3 neutropenia occurred in 14%of patients, whereas grade 3/4 thrombocytopenia was seen in only 4%.One patient died of complications of a severe allergic reaction.Conclusion: Combination treatment using paclitaxel and carboplatin isactive and well tolerated in patients with inoperable non-small-cell lungcancer. The dose-response relationship to paclitaxel and results of comparisonwith other platinum-based regimens remain to be determined.     

First-line chemotherapy with paclitaxel by three-hour infusion and carboplatin in advanced breast cancer (final report): A phase II study conducted by the Hellenic Cooperative Oncology Group

Purpose: To evaluate the activity and toxicity of the combination of paclitaxel given by three-hour infusion, and carboplatin as first-line chemotherapy in patients with advanced breast cancer (ABC).Background: Paclitaxel is an active agent in ABC. Furthermore, our group has shown that the combination of paclitaxel and carboplatin is effective in anthracycline-resistant ABC.Patients and methods: From January 1996 until March 1997, 66 women with ABC were treated with paclitaxel (175 mg/m²) by three-hour infusion followed by carboplatin at an AUC of 6 mg × min/ml every three weeks. The median age of the patients was 56 years (range 28–75). A total of 39 patients had received adjuvant chemotherapy and 22 of them were treated with an anthracycline or mitoxantrone-containing regimen.Results: A total of 324 cycles (median: six) were administered, 273 (85%) of them at full dose. The median number of delivered cycles was six. The median delivered dose intensity (DI) of paclitaxel was 55.1 mg/m²/week (range 30.5–69.3) and the relative DI was 0.95 (range 0.5–1.2). Eight patients (12%, 95% confidence interval (CI): 5%–22%) achieved complete and 28 (42%, 95% CI: 30%–55%) partial responses. Grade 3–4 toxicities included anemia (5%), granulocytopenia (24%), thrombocytopenia, nausea/vomiting and allergic reaction (3% each), myalgias/arthralgias and neurotoxicity (1,5% each). Febrile neutropenia occurred in eight (12%) patients. Alopecia was universal. After a median follow-up of 17.3 (range 0.07–24.5) months, 48 (72%) patients have demonstrated tumor progression and 24 (36%) have died. Median time to progression was 8.6 (range 0.07–23+) months and median survival 20.4 (range 0.07–24.5+) months.Conclusions: The combination of paclitaxel and carboplatin has moderate activity in ABC and can be easily delivered on an outpatient basis with manageable toxicity. This regimen may be useful especially in patients to whom anthracyclines or cisplatin administration is precluded because of other concomitant diseases.     

A randomized phase II trial comparing every 3-weeks carboplatin/paclitaxel with every 3-weeks carboplatin and weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: The optimal schedule of taxane administration has been an area of active interest in several recent clinical trials. METHODS: To address a pure schedule question, we randomized 161 patients with advanced stage IIIB or IV non-small-cell lung cancer (NSCLC) to either paclitaxel 225 mg/m2 every 3 weeks x 4 cycles or 75 mg/m2/week x 12 (cumulative dose on each arm = 900 mg/m2). Both arms received concurrent carboplatin AUC 6 every 3 weeks x 4 cycles. RESULTS: The two arms were well-balanced in terms of known prognostic factors. The overall response rate and survival outcomes were similar on the two arms. There was significantly more grade 3/4 thrombocytopenia and grade 2-4 anemia on the weekly arm but less severe myalgias/arthralgias and alopecia. No difference in the rates of peripheral neuropathy was observed; however, patients on the every 3 weeks arm reported significantly more taxane therapy-related side-effects on the functional assessment of cancer therapy taxane subscale. CONCLUSIONS: This randomized trial exploring schedule-related issues with carboplatin/paclitaxel confirms the versatility of this regimen.     

Weekly dose-dense paclitaxel and carboplatin in recurrent ovarian carcinoma: A phase II trial

PurposeThe aim of this study was to investigate efficacy and toxicity of the dose-dense weekly paclitaxel (T) and carboplatin (C) in the management of platinum-resistant/sensitive recurrent epithelial ovarian cancer (EOC) previously treated with 3 weekly paclitaxel/carboplatin.MethodsThirty two patients with recurrent EOC who had received 3 weekly TC before were enrolled. Nine patients relapsed within 6 months (platinum-resistant), 13 patients relapsed after 12 months (platinum-sensitive) and in 10 patients recurrence occurred between 6 and 12 months (intermediate platinum-sensitive). Weekly (T) at a dose of 80 mg/m², followed by weekly (C) AUC 2 on day 1, 8, and 15 of a 28-day cycle for 6 planned cycles were administrated. End-points were overall response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity.ResultsThe ORR was 62.5%. For the platinum-resistant, intermediate platinum-sensitive and platinum-sensitive patients the ORR was 44.4% (4/9), 60% (6/10) and 76.9% (10/13), respectively, and 1 (11.1%), 2 (20%) and 5 (38.46%) patients, respectively had CR. PFS was 9.1 months (6.13, 9.1 and 12.17 months, for the 3 groups, respectively) (P < 0.001). OS was 14 months (9.17, 15.2, and 19.23 months, for the 3 groups, respectively) (P < 0.001). Treatment-related adverse events were manageable with only 1 patient (3.1%) suffering from grade 4 neutropenia. Grade 3 hematological and non-hematological toxicities were neutropenia in 8 (25%), and peripheral neuropathy in 4 (12.5%) patients, respectively.ConclusionWeekly TC is active and well-tolerated in platinum-resistant and platinum-sensitive patients with recurrent EOC previously treated with TC given every 3 weeks.     

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer

A total of 53 women with chemotherapy-na?ve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.     

Phase I/II study of the combination of carboplatin and paclitaxel as first-line chemotherapy in patients with advanced epithelial ovarian cancer

Purpose: We performed a phase I/II study evaluating the combination ofpaclitaxel and carboplatin as first-line chemotherapy in patients withadvanced ovarian cancer. The aim of this study was to define a feasible andsafe combination regimen that could be recommended for future phase IIIstudies.Design: This study was a parallel two-arm, non-randomized, open trial. Ina first step, carboplatin was administered at a fixed dose of AUC 5 andpaclitaxel was escalated in 25 mg/m² steps starting at 135mg/m². Paclitaxel was given as a three-hour infusion.Carboplatin was administered on day 1 following paclitaxel in one study armand 24 hours after paclitaxel infusion on day 2 in the other study arm.Carboplatin was escalated to AUC 6 and AUC 7.5 after the MTD for paclitaxelhad been defined. Treatment was repeated every three weeks.Patients: Sixty-one patients with untreated histologically confirmedepithelial ovarian cancer were recruited of whom 59 were found eligible andevaluable for toxicity. Thirty-three patients with bidimensionally measurabledisease were evaluable for tumor response.Results: We could not detect any advantage of the two-day schedule comparedwith the more convenient one-day schedule. Dose limiting toxicities wereneutropenia, thrombocytopenia, and neurotoxicity. Except for two patients,toxicity was acceptable and clinically managable. One patient died ofneutropenic sepsis and one further patient developed grade III peripheralneurotoxicity that did not resolve within two months after chemotherapy hadbeen terminated. Overall objective response rate was 70%. The MTD forpaclitaxel was 185 mg/m² and AUC 6 for carboplatin,respectively. Secondary prophylaxis with G-CSF did not allow further doseescalation and therefore is not generally recommended.Conclusions: Paclitaxel 185 mg/m² given as three-hourinfusion followed by carboplatin AUC 6 is a feasible and safe regimen and canbe recommended for phase III trials. Observed response rates justify furtherevaluation of this combination. A randomized phase III trial comparing athree-hour infusion of paclitaxel 185 mg/m² combined witheither carboplatin AUC 6 or cisplatin 75 mg/m² as first-linechemotherapy of advanced ovarian cancer has recently been initiated by ourgroup.     

Phase II study of the combination carboplatin and paclitaxel in patients with ovarian cancer

Background: Recently the feasibility of combining carboplatin withpaclitaxel has been demonstrated in dose-finding studies. Maximum tolerateddoses were 550 mg/m² and 200 mg/m² (threehours), respectively. We report now a phase II study in ovarian cancerpatients.Patients and methods: Twenty-one chemo-naïve patients with optimally(n = 6) or suboptimally (n = 15) debulked stage III or IV ovarian cancer weretreated every three weeks for six courses with paclitaxel (200mg/m²) as a three-hour infusion, immediately followed bycarboplatin (550 mg/m²) as a 30-minute infusion.Results: Uncomplicated neutropenia was the principal toxicity, with mildanemia occurring regularly. As observed in the preceding phase I study, arelative lack of thrombocytopenia, generally grade III was found. Othertoxicities consisted of mild neurotoxicity, nausea and vomiting, alopecia,myalgia, and bone pain. All suboptimally debulked patients responded totherapy. Overall, 12 patients underwent second-look laparoscopy, whichrevealed a pathologically confirmed complete remission in six. The medianfollow-up interval at the time of analysis was 14 months. Twelve patients arecurrently free of progression, at 8+ to 19± months after the start oftherapy.Conclusion: The carboplatin/paclitaxel combination appears to be awell-tolerated regimen, yielding high response rates. This combination has nowgone forward to be evaluated in prospective randomized trials versus thecisplatin/paclitaxel combination.     

Phase II study of paclitaxel and carboplatin in advanced gastric cancer previously treated with 5-fluorouracil and platinum

BACKGROUND: The combination of paclitaxel and carboplatin has been used to treat patients with many types of tumor, including gastric cancer. We evaluated the efficacy and safety of this combination in advanced gastric cancer patients previously treated with 5-fluorouracil and platinum. METHODS: Patients who had pathologically been proven to have measurable lesions were treated with paclitaxel (200 mg/m(2) for 3 h) and carboplatin [area under the concentration-time curve (AUC = 6)] on day 1 and in 21 day cycles. RESULTS: A partial response was achieved in 10 of 45 patients [22%, 95% confidence interval (CI), 10-34]. Of the 32 patients previously treated with cisplatin, four (13%) achieved partial response, whereas, of the 13 patients previously treated with heptaplatin, six (46%) achieved partial response. In all patients, the median time to progression was 14 weeks (95% CI, 10-18), and the median overall survival was 32 weeks (95% CI, 26-38). The most common grade 3/4 adverse events were neutropenia (40% of patients) and neuropathy (2.2%). Two patients developed neutropenic fever. However, there were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with paclitaxel and carboplatin is feasible in patients with advanced gastric cancer who were previously treated with 5-fluorouracil and platinum.     

Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: To compare survival between patients with advanced breast cancer (ABC) treated with epirubicin/paclitaxel (Taxol) or paclitaxel/carboplatin (Cp) chemotherapy. PATIENTS AND METHODS: From January 1999 to April 2002, 327 eligible patients with ABC were randomized to receive either paclitaxel 175 mg/m(2) in a 3-h infusion followed by epirubicin (EPI) 80 mg/m(2) (group A) or paclitaxel, as in group A, followed by Cp at an AUC of 6 mg x min/ml (group B) every 3 weeks for six cycles. RESULTS: After a median follow-up of 23.5 months, median survival was not significantly different between the two groups (22.4 months versus 27.8 months, P=0.25), whereas median time to treatment failure was significantly longer in patients treated with paclitaxel/Cp (8.1 months in group A versus 10.8 months in group B, P=0.04). Both regimens were well tolerated. In total, 39 patients (24%) in group A and 46 (29%) in group B suffered at least one severe side-effect. Quality-of-life assessment and cost analysis did not reveal any significant differences between the two groups. CONCLUSION: Our study suggests that the paclitaxel/Cp combination is an effective therapeutic alternative for patients with ABC in which anthracycline administration has the potential of being harmful.     

A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2); doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2) and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2), doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome.     

紫杉醇联合卡铂治疗晚期非小细胞肺癌的临床观察

目的:评价紫杉醇联合卡铂化疗方案治疗晚期非小细胞肺癌的近期疗效和不良反应.方法: 25例晚期非小细胞肺癌,应用紫杉醇150mg-175mg/m2、卡铂按浓度/时间曲线下面积(AUC)＝5给药联合化疗,每3周重复,进行3-4周期.结果: 全组CR 0例,PR 12例,SD 10例,PD 3例,总有效率48 %,不良反应主要为关节肌肉酸痛、骨髓抑制、轻度胃肠道反应、脱发.结论: 紫杉醇联合卡铂治疗晚期非小细胞肺癌疗效较好,不良反应可耐受,有较好的临床应用价值.     

Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer. A phase III study of the Hellenic Cooperative Oncology Group.

BACKGROUND: This phase III study was designed to compare the combination paclitaxel (Taxol)-gemcitabine (PG) versus carboplatin-gemcitabine (CG) in patients with advanced inoperable non-small-cell lung cancer. METHODS: Chemotherapy-naive patients with performance status of zero or one were randomized to gemcitabine 1 gm/m(2) on days 1 and 8 plus either paclitaxel 200 mg/m(2) on day 1 (arm A) or carboplatin at an area under the concentration-time curve of 6 mg on day 1 (arm B) every 3 weeks. Primary end point was overall survival (OS). Secondary end points included objective response (OR), time to progression and toxicity. RESULTS: A total of 512 patients were enrolled and 452 eligible (arm A, 225; arm B, 227) were analyzed. All characteristics were well balanced with the exception of vena cava obstruction symptoms and lymph node involvement. Median survival was 9.97 months [95% confidence interval (CI) 8.74-12.0] for group A and 10.49 (95% CI 9.04-11.94) for group B. There was no difference in the OS, 1-year survival, OR and TtP. However, statistically significant differences were seen in toxicity. CONCLUSION: The two regimens are equally active. Myelotoxicity is worse in the CG group whereas alopecia, myalgia and neurotoxicity worse in the PG group.     

Phase I/II investigation of paclitaxel, ifosfamide and carboplatin for advanced non-small-cell lung cancer.

BACKGROUND: The aim of this study was to evaluate feasibility and tolerability of the three-drug combination of paclitaxel, ifosfamide and carboplatin (TIC) in patients with advanced non-small-cell lung cancer. The specific objectives of the study were: (i) to define the dose-limiting toxicities (DLTs) and the maximum-tolerated dose of ifosfamide administered as part of the combination; and (ii) to determine the overall response rate and overall survival of patients treated with this regimen. PATIENTS AND METHODS: Patients with untreated, stage IIIB (pleural effusion) or stage IV non-small-cell lung cancer were enrolled in one of three cohorts. Patients received paclitaxel 200 mg/m(2) as a 1-h infusion on day 1 with carboplatin at an area under the concentration-time curve (AUC) of 6 mg.min/ml on day 2. For dose level I, ifosfamide was administered at a dose of 2 g/m(2) on days 1 and 2. For dose levels II and III, the dose of ifosfamide was decreased to 1.5 g/m(2) on days 1 and 2 and the dose of carboplatin was decreased to AUC 5 mg.ml/min. Therapy for dose levels I and III included filgrastim support (5 micro g/kg/day), which was initiated on day 3 and continued until after day 11 or until an absolute neutrophil count >10 000/ micro l. Treatment cycles were repeated every 21 days. Once the phase II dose was established, a full cohort of patients received therapy at this dose level to examine further the regimen's activity and tolerability. RESULTS: Neutropenia was the DLT encountered for dose levels I and II. No DLT was encountered in the initial six patients treated at dose level III, and therefore this dose level was declared the recommended phase II dose. A total of 49 patients were treated at the recommended phase II dose. The predominant non-hematological toxicity encountered with this triplet regimen was cumulative peripheral neuropathy. Of the 65 eligible patients enrolled in this study, 17 (26%) responded. There were 15 patients with partial responses (23%), two with regression, and 26 with stabilization of disease (40%). Median progression-free and overall survival were 4.8 and 9.4 months, respectively. CONCLUSIONS: The combination TIC is well-tolerated. This triplet regimen produced response and survival rates in advanced non-small-cell lung cancer similar to those of other current combination chemotherapy regimens.     

紫杉醇脂质体联合卡铂治疗晚期卵巢上皮癌的临床分析

目的研究紫杉醇脂质体联合卡铂方案化疗治疗晚期卵巢上皮癌的临床疗效和毒副作用。方法对经减瘤术后病理组织学确诊的Ⅲ一Ⅳ卵巢上皮癌患者26例,采用紫杉醇脂质体联合卡铂方案化疗,其中紫杉醇脂质体130～175mg／m^2第1天静脉滴注;卡铂300mg／m^2第2天静脉滴注,每21天为1个周期,每2个周期评价1次疗效。结果26例患者完全可以评价疗效,其中完全缓解7例,部分缓解11例,稳定6例,进展3例,总有效率为69．23％,其中Ⅲ期有效率为72．22％,Ⅳ期有效率为62．50％。中位疾病进展时间（MTYP）10个月（5～13个月）,无复发生存期5个月。毒副作用主要为骨髓抑制和胃肠道反应。结论紫杉醇脂质体联合卡铂方案治疗晚期卵巢上皮癌近期疗效好,毒副作用可以耐受,值得临床推广使用。     

Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid tumours

Background:

As a prelude to combination studies aimed at resistance reversal, this dose-escalation/dose-expansion study investigated the selective Src kinase inhibitor saracatinib (AZD0530) in combination with carboplatin and/or paclitaxel.

Methods:

Patients with advanced solid tumours received saracatinib once-daily oral tablets in combination with either carboplatin AUC 5 every 3 weeks (q3w), paclitaxel 175 mg m⁻² q3w, paclitaxel 80 mg m⁻² every 1 week (q1w), or carboplatin AUC 5 plus paclitaxel 175 mg m⁻² q3w. The primary endpoint was safety/tolerability.

Results:

A total of 116 patients received saracatinib 125 (N=20), 175 (N=44), 225 (N=40), 250 (N=9), or 300 mg (N=3). There were no clear dose-related trends within each chemotherapy regimen group in number or severity of adverse events (AEs). However, combining all groups, the occurrence of grade ⩾3 asthenic AEs (all causality) was dose-related (125 mg, 10% 175 mg, 20% ⩾225 mg, 33%), and grade ⩾3 neutropenia occurred more commonly at doses ⩾225 mg. There was no evidence that saracatinib affected exposure to carboplatin or paclitaxel, or vice versa. Objective responses were seen in 5 out of 44 patients (11%) receiving carboplatin plus paclitaxel q3w, and 5 out of 24 (21%) receiving paclitaxel q1w.

Conclusion:

Saracatinib doses up to 175 mg with paclitaxel with/without carboplatin showed acceptable toxicity in most patients, and are suitable for further trials.     

Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer: a phase II study from Indiana University.

Background: Recombinant human angiostatin (rhAngiostatin) functions as a potent inhibitor of angiogenesis. This study combined rhAngiostatin with a standard chemotherapy regimen in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: Eligible patients had chemotherapy-naïve stage IIIB (with pleural effusion) or IV NSCLC, performance status (PS) 0 or 1, no history of bleeding, brain metastasis or requirements for anti-coagulation. Patients received carboplatin (AUC 5) intravenously and paclitaxel (175 mg/m²) intravenously day 1 + subcutaneous rhAngiostatin at either 15 mg or 60 mg twice daily. Cycles were repeated every 3 weeks, for up to six cycles. Patients without progression after completing at least four cycles were continued on maintenance rhAngiostatin until disease progression.Results: Patient characteristics (n = 24) were: 16 males, median age 66 years (range 45–78), 54% PS 1, 83.3% stage IV and 62.5% adenocarcinoma. Grade 3/4 toxicities included: fatigue 47.8%, neutropenia 39.1%, dyspnea 39.1%, vascular 26.1% and infection 17.4%. The overall response rate was 39.1%, 39.1% stable disease and 21.7% progressive disease. Median time to progression was 144 days, and 1-year survival was 45.8%.Conclusions: rhAngiostatin in combination with paclitaxel and carboplatin is feasible and results in a high disease control rate in patients with advanced NSCLC.     

紫杉醇联合卡铂治疗晚期非小细胞肺癌的临床观察

目的：评价紫杉醇联合卡铂化疗方案治疗晚期非小细胞肺癌的近期疗效和不良反应。方法：25例晚期非小细胞肺癌,应用紫杉醇150mg-175mg／m^2、卡铂按浓度／时间曲线下面积（AUC）=5给药联合化疗,每3周重复,进行3—4周期。结果：全组CR0例,PR12例,SD10例,PD3例,总有效率48％,不良反应主要为关节肌肉酸痛、骨髓抑制、轻度胃肠道反应、脱发。结论：紫杉醇联合卡铂治疗晚期非小细胞肺癌疗效较好,不良反应可耐受,有较好的临床应用价值。     

Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: A single centre prospective phase II trial

Nimotuzumab (N) is a humanized anti‐epidermal growth factor receptor monoclonal antibody. This prospective, single‐armed, open label phase II study was conducted to evaluate the efficacy and safety of the combination of paclitaxel (T)/cisplatin (P) with nimotuzumab (N) as first‐line treatment in advanced esophageal squamous cell carcinoma (ESCC). Patients with pathologic confirmed unresectable locally advanced or metastatic ESCC were treated with the TPN regimen: nimotuzumab 200 mg weekly, paclitaxel 175 mg/m² on day 1 and cisplatin 30 mg/m² on days 1 and 2; repeat cycle every 3 weeks for six cycles. Radiotherapy was allowed to be admitted after four cycles of TPN treatment. The primary endpoint was the objective response rate (ORR). The secondary endpoint was the overall survival (OS), duration of disease control (DDC) and toxicities. From March 2011 to April 2013, a total of 59 patients were enrolled and 56 were eligible for the final analysis. Overall RR was 51.8% and disease control rate (DCR) (CR + PR + SD) was 92.9%. Local treatment (radiotherapy or surgery) followed by chemotherapy improved the duration of disease control for patients with metastatic disease and local‐regional advanced disease to 8.2 months and more than 23 months, respectively. The OS for patients with metastatic disease was 14.0 months (95% CI: 6.8–21.2 months). The most common G3/4 toxicities were neutropenia (46.4%), nausea (48.3%), alopecia (78.6%), anorexia (42.8%), vomiting (55.4%), arthralgia (62.5%) and anorexia (5%). Adding nimotuzumab to the standard TP regiment was safe, and well tolerated. The TPN regimen is an effective combination as the first‐line chemotherapy for the patients with advanced ESCC, and appears more active than current standard regimens.     

紫杉醇联合奈达铂治疗晚期食管癌的临床观察

目的：观察紫杉醇（PTX）联合奈达铂（NDP）治疗晚期食管癌的临床疗效和不良反应。方法：晚期食管癌患者51例,紫杉醇135—175mg／m^2,静脉滴注,第1天;奈达铂80—100mg／m^2,加入生理盐水500ml中静滴2h,第2天;21天为1周期,连用2个周期后评价疗效。结果：全组50例可评价疗效,总有效率58．0％（29／50）,完全缓解3例,部分缓解26例,中位生存期为9．8个月,中位疾病进展时间5．7个月,中位缓解时间4．5个月。主要不良反应为骨髓抑制所致的血小板及白细胞减少,消化道反应轻,未发现肝肾功能损害。结论：紫杉醇联合奈达铂治疗晚期食管癌近期疗效高,安全性较好,患者可耐受,值得临床观察应用。