Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer.

PURPOSE: Stealth (ALZA Corporation, Palo Alto, CA) liposomal drug formulation allows a higher intratumoral accumulation and a prolonged plasma half-life of the encapsulated drugs. In the study presented here, we evaluated the feasibility of Stealth liposomal doxorubicin (Caelyx; ALZA Corporation) administered concurrently with conventionally fractionated radiotherapy in the treatment of non-small-cell lung cancer (NSCLC) and head and neck cancer (HNC). PATIENTS AND METHODS: Fifteen patients with NSCLC and 15 with squamous-cell HNC were recruited in two phase I dose-escalation trials. The starting dose of Caelyx was 10 mg/m(2) every 2 weeks (for three cycles during radiotherapy) and was increased by 5 mg/m(2) dose increments for every three patients. RESULTS: The maximum tolerated dose of Caelyx was 20 mg/m(2) for HNC and 25 mg/m(2) in NSCLC patients. Oral/pharyngeal mucositis was the dose-limiting toxicity for HNC patients. "In field" radiation skin toxicity was slightly increased. Hematologic toxicity was minimal. Single photon emission computed tomographic evaluation of Caelyx distribution, using technetium-99m-diethylenetriamine pentaacetic acid labeling, revealed a high intratumoral accumulation of the drug. The tumor to thoracic vessel area count ratio in the NSCLC cases ranged from 0.6 to 1.6 (mean +/- SD, 1.01 +/- 0.29), whereas this ratio was higher (0.8 to 1.85; mean +/- SD, 1.35 +/- 0.39) in HNC cases (P =.049). The complete response rate was 21% in the NSCLC cases and 75% in the HNC cases. NSCLC cases with higher Caelyx tumor accumulation responded better to the regimen. The tumor microvessel density assessed with the anti-CD31 monoclonal antibody directly correlated with the degree of the Caelyx accumulation (P =.007; r =. 92). CONCLUSION: We conclude that combination of radiotherapy with Stealth liposomal doxorubicin is feasible. The potential role of such a regimen in the treatment of highly angiogenic tumors requires further investigation.     

Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small cell lung cancer

BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles. RESULTS: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.     

康莱特注射液联合同步放化疗治疗68例中晚期非小细胞肺癌临床观察

目的：：观察康莱特注射液配合同步放化疗对局部晚期非小细胞肺癌（NSCLC）的疗效和不良反应。方法：68例Ⅲ期NSCLC患者随机分为二组：治疗组（同步放化疗＋康莱特注射液）35例,同步放化疗中放疗采用三维适形放疗技术,DT60-66Gy/30-33f/6-7W。化疗采用EP方案,依托泊苷50mg/m2,1次/日,d1-5,d29-33;顺铂50mg/m2,1次/日,d1、8、29、36。同步放化疗同时联合康莱特注射液2周期,每周期为200ml静脉滴注,1次/日,连续21天,休息7-10天进行第2周期。对照组33例只行同步放化疗,放化疗方式同治疗组。治疗完成后评价疗效和不良反应。结果：治疗组总有效率（CR＋PR）74.3%,完全缓解率（CR）22.9%;对照组总有效率51.5%,完全缓解率15.2%,两组间总有效率有显著统计学差异（P〈0.05）。中位生存期治疗组和对照组分别为17个月和13个月,1、2年生存率治疗组分别为62.9%、34.3%;对照组分别为51.5%、27.3%,两组间差异无显著性（P〉0.05）。不良反应主要是放射性肺炎、放射性食管炎和骨髓抑制,两组间差异无显著性。结论：康莱特注射液联合同步放化疗可明显提高局部晚期非小细胞肺癌（NSCLC）的近期疗效,远期疗效略有提高,但无统计学差异。     

Pegylated liposomal doxorubicin in combination with mitomycin C, infusional 5-fluorouracil and sodium folinic acid. A phase-I-study in patients with upper gastrointestinal cancer

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (FU) plus folinic acid (FA) is an effective treatment for metastatic gastrointestinal cancer. Anthracyclines are commonly used in the treatment of upper gastrointestinal cancer. The aim of this study was to determine the maximum tolerated dose of liposomal, pegylated doxorubicin (Caelyx) in combination with infusional 5-FU/sodium FA and MMC. Escalating doses of Caelyx (15-25-30-35 mg m(-2) corresponding to dose levels I-IV) were applied on days 1 and 29, given to fixed doses of 24-h 5-FU (2000 mg m(-2)) and sodium FA (500 mg m(-2), mixed with 5-FU in one pump) weekly for 6 weeks, and MMC 7 mg m(-2) on days 8 and 36. At least three patients were treated at each dose level. A total of 25 patients are evaluable. No dose-limiting toxicity (DLT) was observed on level I (n=3). On level II, DLT occurred in three out of five patients (mucositis and leucopenia). Owing to the early DLTs at this dose, we added a 20 mg m(-2) Caelyx dose level (Ia). In total, 17 patients were treated at this dose level. Among these, only two patients experienced DLT in cycle one and 37 complete cycles have been administered in association with a low toxicity profile. The median dose intensity was 100% for each drug during the first course and no treatment delay exceeding 7 days was required. The recommended dose of 4-weekly Caelyx in combination with weekly 24-h 5-FU/sodium FA and 4-weekly MMC is 20 mg m(-2). Preliminary antitumour activity has been observed in patients with pretreated pancreatic cancer and in untreated gastric cancer.     

High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas--rationale for combination with radiotherapy

Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth liposomal doxorubicin (Caelyx) is a novel drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy with Caelyx in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a total dose of 70 Gy. Caelyx was given as a 30-min infusion at a dose of 25 mg/m2 every 2 weeks. Scintigraphic imaging with Caelyx-99mTc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation compared to the surrounding healthy tissue. The regimen was well tolerated without any severe hematological or systemic toxicity. 'In field' radiation toxicity was not increased. Complete response was observed in 4/7 cases. It is concluded that combined chemo-radiotherapy with stealth liposomal doxorubicin for locally advanced sarcomas is feasible and promising, the benefit expected from the unique ability of the stealth liposomes to accumulate selectively in the tumoral tissue.     

Phase II study of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy for patients with squamous cell cancer of the head and neck

A phase II trial of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy was conducted in 20 patients with treatment-na?ve squamous cell cancer of the head and neck (SCCHN). 10 patients received two cycles of Caelyx (40 mg/m(2)) every 3 weeks before starting radical radiotherapy (RT). Subsequently, consecutive groups of 3 patients received a third escalating dose of Caelyx (10, 15 and 20 mg/m(2)) 3 days before RT. 9 of 18 (50%, 95% confidence intervals (CI): 26-74%) evaluable patients responded to Caelyx, with 11 responses in 26 (42%, 95% CI: 24-62%) evaluable sites (three complete responses (12%), eight partial responses (31%)). There was no grade 3/4 haematological, mucosal or cardiac toxicity. Nausea and vomiting were minimal. There were no drug-related RT delays. Local RT-induced toxicity was not increased. Caelyx has significant activity against SCCHN and warrants further investigation in this disease. In view of its tumour targeting properties and activity at moderate doses, it may be useful in concomitant chemoradiotherapy strategies for SCCHN.     

Thoracic radiotherapy and daily vinorelbine as radiosensitizer in locally advanced non small cell lung cancer: a phase I study

Experimental studies have shown that vinorelbine is a powerful radiosensitizer in vitro. To date, no reports on clinical activity of the single agent vinorelbine as radiosensitizer have been published. The aim of the present phase I study was to determine the maximum tolerated dose (MTD) of vinorelbine administered daily concurrently with thoracic radiotherapy, with or without amifostine support, in the treatment of locally advanced non small cell lung cancer. In vitro studies have shown that vinorelbine can potentiate the antitumor effects of radiation therapy. Amifostine is a sulphydril compound that has shown to protect normal tissues from chemotherapy and radiotherapy-induced toxicities. Radiotherapy lasted 6 weeks and the total dose was 55 Gy. The daily fraction was 1.8 Gy, administered 5 days a week for 5 weeks and increased to 2.0 Gy during the sixth and last week. Concurrent vinorelbine was administered daily with a planned escalation of the dose from 4, to 5 and 6 mg/m(2). Fourteen patients were enrolled in the study. The first dose of vinorelbine was 4 mg/m(2) and it showed to be feasible without dose-limiting toxicity (DLT). Instead, the second dose level of 5 mg/m(2) was unfeasible because three out of six patients had DLT (grade 4 neutropenia, treatment interruption longer than 2 weeks for prolonged grade 2 neutropenia and treatment interruption longer than 2 weeks for prolonged grade 3 esophagitis together with grade 4 dyspnea). At that time, the study continued adding amifostine to vinorelbine in order to increase its MTD. Amifostine was administered by means of subcutaneous injection 15 min before each radiotherapy fraction at the fixed dose of 300 mg/m(2). However, 5 mg/m(2) of vinorelbine were considered unfeasible even with amifostine support because three out of five patients showed DLT (grade 4 neutropenia, febrile grade 4 neutropenia and grade 3 liver toxicity). Among 14 patients enrolled in the study, eight completed the planned treatment because six patients experienced DLT, which determined treatment interruption. Overall, four partial and two complete responses were observed. Two partial and one complete response were observed in those three patients who had been treated with the first dose of vinorelbine. In conclusion, our data show that the MTD of daily vinorelbine is 4 mg/m(2). Therefore, this is the recommended dose of daily vinorelbine to be administered with concurrent thoracic radiotherapy in a phase II trial. Finally, amifostine administered subcutaneously failed to increase the MTD of daily vinorelbine.     

Phase I study of combination chemotherapy with gemcitabine and irinotecan for non-small cell lung cancer

A phase I study combining a fixed dose of gemcitabine with differing doses of CPT-11 every two weeks for previously treated non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A total of 21 patients with previously treated non-small cell lung cancer were treated every two weeks with CPT-11 followed by gemcitabine. The gemcitabine dose was fixed at 1000 mg/m2. The starting dose of CPT-11 (50 mg/m2) was then escalated different patients in 25 mg/m2 increments until 150 mg/m2 (level 5), the recommended dose as a single agent in Japan. RESULTS: Dose-limiting toxicity was only observed at level 5, in three of nine patients receiving the highest dose of CPT-11. One patient had grade 3 diarrhea, and two could not continue chemotherapy with grade 1 diarrhea or grade 1 neutropenia on day 15. Hematologic toxicity with this combination regimen, however, was generally mild. No grade 4 neutropenia, and only one case of grade 3 leukopenia was noted at level 5. Compliance with the combination regimen was good and there was no cumulative toxicity with the subsequent courses. Twenty-five courses of therapy were given at level 5 and the percentage of actual delivered doses/planned doses was 82%. CONCLUSIONS: The combination chemotherapy has only very mild toxicity and dose which can be recommended with this regimen are 1000 mg/m2 for gemcitabine and 150 mg/m2 for CPT-11 every two weeks.     

紫杉醇每周疗法联合顺铂治疗晚期非小细胞肺癌

目的:观察紫杉醇联合顺铂治疗晚期非小细胞肺癌(NSCLC)的临床疗效和毒副反应。方法:晚期NSCLC患者共32例,紫杉醇60mg/m2,第1、8、15天,静脉输注3小时。顺铂25mg/m2,静脉输注2小时,第2、3、4天,28天为1周期,至少治疗2周期。结果:全组32例中,CR2例,PR13例,NC14例,PD3例,有效率46.9%(15/32),毒性反应主要为骨髓抑制,脱发、神经毒性及恶心、呕吐等,患者均可耐受。结论:紫杉醇每周疗法联合顺铂治疗晚期NSCLC是一个疗效高,毒副作用可耐受的好方案。     

A dose escalation study of paclitaxel and carboplatin in untreated Japanese patients with advanced non-small cell lung cancer.

BACKGROUND: The combination of paclitaxel (225 mg/m(2), 3-h infusion) and carboplatin (area under the curve 6) is widely used for non-small cell lung cancer in the USA. In Japan, however, the recommended dose for single-use paclitaxel in 3-h infusion is 210 mg/m(2) and the optimal dose of this agent in combination with carboplatin has not been established. This dose escalation study was designed to determine the maximum tolerated dose of paclitaxel in 3-h infusion plus carboplatin at a fixed dose of area under the curve 6 for Japanese patients with advanced, untreated non-small cell lung cancer. METHODS: Between October 1999 and May 2000, 19 patients were enrolled and 18 of these patients were evaluable for toxicity. Chemotherapy consisted of carboplatin area under the curve 6 and an escalated dose of paclitaxel on day 1 every 3-4 weeks. The initial dose of paclitaxel was 175 mg/m(2) and was increased by 25 mg/m(2) at each dose level. RESULTS: Neutropenia was the major toxicity observed, but was not dose related. Febrile neutropenia was not observed. No grade 3 or more peripheral neuropathy, myalgia or arthralgia was reported. The maximum tolerated dose was not determined even at the highest paclitaxel dose level (225 mg/m(2)) in this study. Partial responses were observed in six of the 19 patients (31.6%). CONCLUSION: We conclude that paclitaxel at 225 mg/m(2) in 3-h infusion and carboplatin area under the curve 6 can safely be given to Japanese patients with non-small cell lung cancer.     

Sequential chemo- and radiochemotherapy with weekly paclitaxel (Taxol) and 3D-conformal radiotherapy of stage III inoperable non-small cell lung cancer. Results of a dose escalation study

The purpose of this study was the determination of the maximum tolerable dose (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radiotherapy in non-small cell lung cancer (NSCLC) and the evaluation of side effects, patient outcome and tumor response. Thirty-eight patients with inoperable NSCLC, UICC-stage IIIA (n=14)/IIIB (n=24) received two cycles of induction chemotherapy with PX/carboplatin followed by combined radiochemotherapy (60 Gy/6 weeks) with weekly PX which was escalated in cohorts of four patients until dose limiting toxicity (DLT) was reached. Starting level was 40 mg/m(2). 3D-conformal radiotherapy was applied in all patients. Toxicity was determined by WHO criteria. Patients were followed-up 3-monthly. Thirty eight patients have entered the study, 34 patients are evaluable. DLT was esophagitis III degrees, requiring interruption of radiotherapy and was reached at the PX 70 mg/m(2). Two hypersensitivity reactions (50 mg/m(2)) and one leucopenia III degrees (60 mg/m(2)) were observed. Only one patient (60 mg/m(2), 50 Gy) completely aborted treatment. The pneumonitis rate was between 21 and 36% but showed no clear correlation with PX dose. Tumor response (PR and CR) defined by CT-scan 6 weeks following radiotherapy was 88% (30/34). The 1- and 2-year survival rate is 73% and 34%. We conclude that the MTD of weekly PX with 60 Gy normofractionated radiotherapy is 60 mg/m(2). The DLT is esophagitis. Response and survival data of this sequential/combined approach are promising. A minor increase of pulmonary toxicity of irradiation is suspected.     

A randomized study evaluating radiotherapy versus chemotherapy in patients with inoperable non-small cell lung cancer

A combination of cisplatin (70 mg/m2 i.v. day one) and etoposide (100 mg/m2 i.v. day one, 200 mg/m2 orally days 2 and 3) repeated every third week to a maximum of 4 cycles were compared with high voltage radiotherapy, 42 Gy given in 15 fractions over a 3-week period to patients with inoperable non-small cell lung cancer (a shield was used in the posterior field to reduce the total spinal dose less than 40 Gy). One hundred and eighteen patients received radiotherapy; the median survival was 10.6 months compared to 10.5 months for the 116 chemotherapy patients (p = 0.81). The objective response rate (CR + PR) was 42% for the radiotherapy and 21% for the chemotherapy group (p = 0.009). At progression it was optional to cross over to the other treatment modality or to receive phase II chemotherapy. Thirty patients primarily treated with radiotherapy and 54 allocated to chemotherapy received second line antineoplastic treatment.     

Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study

PURPOSE: Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer. METHODS AND MATERIALS: Patients from European and American study centers received i.v. amifostine 300 mg/m2 (n = 67) or placebo (n = 65) before carboplatin 70 mg/m2 and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m2 or placebo before radiotherapy on other days. RESULTS: Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments. CONCLUSIONS: The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.     

吉西他滨/长春瑞滨对Ⅲ～Ⅳ期非小细胞肺癌的放射增敏作用

目的探讨放疗联合吉西他滨/长春瑞滨治疗晚期非小细胞肺癌的近期疗效及不良反应。方法 27例Ⅲ～Ⅳ期非小细胞肺癌(non-small cell lung cancer,NSCLC),分为2组,其中吉西他滨组12例和长春瑞滨组15例。放疗前均先给予2个周期"紫杉醇+顺铂"方案诱导化疗,紫杉醇135 mg/m2静脉滴注第1天,顺铂30 mg/m2静脉滴注第1～3天,21天为1个周期。放疗同期予吉西他滨300 mg/m2,第1、8、15、22天,或长春瑞滨20 mg/m2,第1、8、15、22天。放疗均采用三维适形方式。结果完全缓解率(CRR)、部分缓解率(PRR)及总有效率(ORR)分别为3.7%(1/27)、55.6%(15/27)和59.3%(16/27)。其中长春瑞滨组和吉西他滨组CRR、PRR及ORR分别为6.7%(1/15)和0、60.0%(9/15)和50.0%(6/12)、66.7%(10/15)和50.0%(6/12)。肺、食管及血液毒性均未出现严重损伤,27例患者均顺利完成放疗。结论放疗联合吉西他滨/长春瑞滨治疗Ⅲ～Ⅳ期非小细胞肺癌近期疗效较好,不良反应均能耐受。远期疗效有待进一步随访。     

Weekly docetaxel with concurrent radiotherapy in locally advanced non-small cell lung cancer: a phase I/II study with 5 years' follow-up

This Phase I/II study investigated weekly docetaxel (Taxotere) with concurrent radiotherapy in 42 patients with untreated stage III non-small cell lung cancer (NSCLC). All patients were treated with chest irradiation: 2Gy administered 5 days/week for 5 weeks, to a total of 50Gy. Docetaxel (1-h infusion) was administered on days 1, 8, 22, and 29< or =2 h before radiation fractions 1, 6, 16, and 21 (i.e. every week excluding the third week of treatment). In the Phase I study (n=12), docetaxel was started at 20 mg/m2 per week (n=3) and escalated in 10 mg/m2 increments (30 mg/m2, n=3; 40 mg/m2, n=6). Dose-limiting toxicity (grade 3-4 esophagitis) occurred with docetaxel 40 mg/m2. The Phase II study (n=30), therefore, evaluated docetaxel 30 mg/m2 (considered recommended dose). All patients except one experienced asymptomatic grade 3-4 lymphopenia; four patients (9.5%) had grade 3-4 esophagitis. The overall response rate was 45.5%, with eight (24.2%) complete responses. The median time to progression at the recommended dose of 30 mg/m2 (n=33) was 12.0 months and the median survival time was 13.6 months. The 1-year survival rate was 60.6%. Five patients (one from Phase I and four from Phase II) were alive after >5 years. In conclusion, weekly docetaxel 30 mg/m2 plus radiotherapy is active and well tolerated in stage III NSCLC.     

尼妥珠单抗联合同期放化疗局部晚期NSCLC的Ⅰ期耐受性研究

目的 探索尼妥珠单抗与同期放化疗联合应用在Ⅲ期NSCLC的可行性与耐受性。方法 选取 18~74岁Ⅲ_A、Ⅲ_B期NSCLC初治患者。尼妥珠单抗分为100、200、400 mg组,每组 3~6例。前 3例如出现 1例剂量限制性毒性(DLT)则再增加 3例,半数出现DLT则停止爬坡。放疗总剂量 60~66 Gy分 30~33次。采用顺铂、依托泊苷联合化疗。同步结束后继续尼妥珠单抗至16周或进展,加或不加同方案化疗2周期。评价不良反应、近期疗效、最佳肿瘤体积退缩情况及生存情况。结果 共入组 9例,7例可检测EGFR表达。3个剂量组均能良好耐受,未有DLT发生。最常见不良反应为血液系统, 3级白细胞减少、粒细胞减少、血红蛋白降低及血小板减少分别为66%、66%、11%、22%;其次为食管炎, 1级44%、2级22%;1级恶心呕吐44%;1级放射性肺炎44%。未发现皮疹或皮肤过敏反应。最佳总体积退缩平均为88%。中位随访时间和中位生存时间26.4个月,1年和 2年OS、DFS、PFS分别为78%和67%、56%和44%、78%和56%。结论 尼妥珠单抗100、200、400 mg每周方案与同期放化疗应用在局部晚期NSCLC可被良好耐受。     

EORTC 10968: a phase I clinical and pharmacokinetic study of polyethylene glycol liposomal doxorubicin (Caelyx, Doxil) at a 6-week interval in patients with metastatic breast cancer. European Organization for Research and Treatment of Cancer.

BACKGROUND: We performed a phase I study of polyethylene glycol (pegylated, Stealth) liposomal doxorubicin (Caelyx, Doxil) using a prolonged (6-week) dose interval to reduce the incidence of skin toxicity that was dose-limiting at more conventional dose intervals, and which appeared to be schedule dependent. PATIENTS AND METHODS: Eligible for the study were metastatic breast cancer patients who had received a maximum of one prior therapy for metastatic disease. The defined dose levels were 60, 70, 80 and 90 mg/m2. RESULTS: Twenty patients were assessed at starting doses of 60 mg/m2 (n = 9) or 70 mg/m2 (n = 11). The dose-limiting toxicity was mucositis. Severe skin toxicity was not observed at the 60 mg/m2 dose level, and occurred in only one patient treated at 70 mg/m2. Significant neutropenia, alopecia, and nausea and vomiting were rare events. No clinical cardiac events occurred, despite a median cumulative doxorubicin dose of 323 mg/m2 (range 5-630 mg/m2). Partial responses were documented in five patients. Pharmacokinetics were assessed in 15 patients, and confirmed the long terminal half-life of the agent (median 77 h) demonstrated in earlier studies. CONCLUSIONS: The recommended dose of Caelyx/Doxil using this schedule is 60 mg/m2 every 6 weeks. This is a safe and effective regimen that permits prolonged administration of anthracycline to patients with metastatic breast cancer.     

Ⅲ期非小细胞肺癌适形放疗加吉西他滨和顺铂同步化疗36例临床疗效观察

Objective: To study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer (NSCLC). Methods: Thirty-six patients with pathologically diagnosed NSCLC received radiotherapy and concurrent chemotherapy. There were 22 patients with stage llla and 14 patients with lllb. Radiotherapy was given a total of 60-70 Gy in conventional fractionation. Chemotherapy included gemcitabine (600 mg/m2) and cisplatin (20 mg/m2), once per week. Results: Thirty-two patients received a total dose of 60-72 Gy. Two patients received 56 Gy and another two patients received 58 Gy. Thirty-four patients received 4-6 weeks of chemotherapy, while two patients received only 2 weeks of chemotherapy. The overall response rate (CR + PR), complete response rate (CR), partially response rate (PR) were 63.3% (30/36), 11.1% (4/36) and 72.2% (26/36) respectively. The median follow-up duration was 18.4 months. The 1-and 2-year overall survival rates were 77.8% (28/36) and 55.6% (20/36),respectively. Conclusion: Concurrent gemcitabine and cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer is effective and well tolerated. Lone-term results need further study.     

Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.     

长春瑞滨联合顺铂治疗晚期非小细胞肺癌38例疗效观察

目的观察NP方案治疗晚期非小细胞肺癌的疗效与毒性。方法应用长春瑞滨25 mg/m2静脉点滴,第1,8天,DDP 80~100mg/m2静脉点滴,第1,2天。结果38例无CR,PR 16例,NC 16例,PD 6例,总有效率42.1%。结论长春瑞滨联合顺铂治疗晚期NSCLC有效率高,毒副反应能耐受。