Preoperative intra-arterial chemotherapy with docetaxel,cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma

The objectives of this study were to evaluate survival in 141 patients with stage II–IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.     

Clinical characteristics of severe peripheral neuropathy induced by docetaxel (Taxotere)

Background: Docetaxel, a semi-synthetic taxane may cause a usuallymild sensory neuropathy. We describe the clinical characteristics of fivepatients who developed a more severe neuropathy following treatment withdocetaxel.Patients and methods: All patients were treated in phase II studieswith 100 mg/m² docetaxel in three weekly cycles, withoutsteroid administration.Results: The clinical picture in these patients was dominated by asensory neuropathy, but in one case severe weakness was present. Anotherpatient developed Lhermitte's sign. Signs and symptoms are usually reversibleafter discontinuation of docetaxel administration, but in three patientssymptoms worsened for some time after the end of treatment before improvementoccurred.Conclusion: Severe docetaxel neuropathy may especially occurfollowing treatment with cumulative dosage over 600 mg/m²; inpatients treated with this dosage a moderate or severe neuropathy may not berare.     

Crystal Structure of 2-Debenzoyl, 2-Acetoxy Paclitaxel (Taxol®): Conformation of the Paclitaxel Side-Chain

Crystals of the C2-acetate analog of paclitaxel, grown from a mixture of isopropyl alcohol and methanol, belong to the space group P2_l with a = 9.058(3), b = 18.306(5), c = 15.043(1) , = 97.09(1)°, Z = 2, V = 2475.1(9)³, D _calc = 1.269 gcm^–3 and µ = 0.75 cm^–1. The structure was determined by direct methods and refined to R(F) = 0.054 and wR(F) = 0.057 for 605 variables and 3496 observed reflections. The paclitaxel side chain possesses a conformation similar to that observed in the crystal structure of docetaxel (Taxotere^®). A three dimensional network of hydrogen bonds is formed through solvent molecules and stabilizes the crystal lattice.     

多西他赛二线治疗23例晚期非小细胞肺癌

目的：评价单药多西他赛[泰索帝)作为二线化疗耐晚期非小细胞肺癌(NSCLC)的疗效和不良反应，方法：23例经病理和(或)细胞学诊断的晚期非小细胞肺癌．曾用含铂类方案化疗，治疗后复发或进展．接受泰素帝75mg/m^2静滴1小时．第1天．每3周重复。结果：可评价疗效23例中．无完全缓解（CR)，部分缓解(PR）17％(4／23)，稳定(SD)57％(13／23)，进展(PD)26％(6／23)，有效率17％(4／23)；中位生存期9个月，一年生存率39％(9，23)。不良反应主要是血液学毒性，但患者可以耐受。结论：泰素帝草药用于二线化疗治疗晚期非小细胞肺癌疗效肯定．耐受性较好。     

A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours.

BACKGROUND: Docetaxel is a widely active cytotoxic agent. The principal dose-limiting toxicities (DLTs) of the 3-weekly regimen are neutropenia and febrile neutropenia. Use of prophylactic granulocyte colony-stimulating factor (G-CSF) may allow higher doses of docetaxel to be administered with potentially greater anticancer efficacy. The objectives of this study were to determine the maximum tolerated dose (MTD) and toxicity profile of docetaxel given with G-CSF support. PATIENTS AND METHODS: Eligible patients had solid tumours and were aged 18-75 years with a WHO performance status of up to 2. Strict criteria for liver function were followed. Patients may have received one previous regimen of chemotherapy in addition to adjuvant chemotherapy. Cohorts of three to six patients received docetaxel over 60-90 min every 3 weeks, commencing at 110 mg/m(2) and escalating at 10 mg/m(2) increments. Patients also received G-CSF 5 micro g/kg/day until neutrophil recovery. A 3-day corticosteroid prophylaxis was given. RESULTS: Twenty-nine patients with median age 55 years (range 29-75) were included. Fourteen (48%) had previously received chemotherapy. At the 170 mg/m(2) dose level (the MTD), two of three patients had DLTs and 160 mg/m(2) was determined to be the recommended dose. The principal DLTs were skin and neurosensory toxicity. Asthenia was frequent, especially at dose levels >/=140 mg/m(2). Grade 4 neutropenia occurred in only 10 patients (35%) and was not dose related, with febrile neutropenia in three patients (10%). CONCLUSIONS: Docetaxel may be escalated considerably above standard doses when administered with G-CSF support. The recommended dose for phase II studies is 160 mg/m(2). With escalated-dose docetaxel, DLTs were non-haematological and qualitatively similar to the toxicity profile at standard doses.     

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: A multicenter phase II study

Purpose: To evaluate the efficacy and safety of the docetaxel-cisplatin combination in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: Chemotherapy-naïve patients with histologically confirmed, measurable stage IIIB or IV NSCLC, a World Health Organization (WHO) performance status of 0–2 and adequate bone marrow, renal, hepatic and cardiac function were eligible for the study. Patients received docetaxel (100 mg/m²) as an one-hour infusion on day 1 and cisplatin (80 mg/m²) as a 30-min infusion with appropriate hydration on day 2. Granulocyte colony-stimulating factor (G-CSF; 150 µg/m² , SC) was given on days 3 to 13. Treatment was repeated every three weeks.Results: Fifty-three patients were enrolled (28 with stage IIIB and 25 with stage IV). One complete and 23 partial responses were observed (overall response rate (OR): 45%; 95% CI: 34.1%–61.8%). The response rate was 57% and 32% in patients with stages IIIB and IV disease (P = NS). The median time to progression was 36 weeks and the median survival 48 weeks; the one-year survival was 48%. Grade 3–4 neutropenia occurred in 23 patients, 15 of whom were hospitalized for neutropenic fever; two patients died of sepsis. Grade 2 neurotoxicity was observed in six patients and grade 3 in five patients; grade 3 fatigue occurred in seven patients, grade 3–4 mucositis in four patients and grade 3–4 diarrhea in six patients. Mild allergic reactions and oedema were observed in five and four patients, respectively. The median dose intensity was 30 mg/m² /week for docetaxel and 24 mg/m² /week for cisplatin, corresponding to 91% and 89% of the specified protocol doses, respectively.Conclusions: The docetaxel–cisplatin combination is an active regimen in advanced NSCLC, but hematologic toxicity remains high despite the prophylactic use of G-CSF.     

高效液相色谱法测定多西紫杉醇注射液含量及其有关物质

目的建立一种反相高效液相色谱法测定多西紫杉醇注射液含量,同时检测其有关物质。方法采用Alltima C18色谱柱(150 mm×4.6 mm,5μm),以甲醇∶20 mmol/L醋酸钠缓冲液(冰醋酸调pH值至5.0)(75∶25,V/V)为流动相,流速1.0 mL/min;检测波长为232 nm,柱温为室温。结果在选定的色谱条件下,多西紫杉醇的分析不受辅料和有关物质的干扰,定量限为500 ng,在25~800μg.mL-1范围内线性关系良好(r=0.999 9);平均加样回收率为99.92%,日内、日间RSD均<4%。结论本法测定多西紫杉醇及其有关物质专属性强,灵敏度高,重现性好,可用于测定注射液中多西紫杉醇的含量和其有关物质检查。     

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial.

BACKGROUND: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks. RESULTS: A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm. CONCLUSIONS: The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.     

Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric cancer.

BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.