Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms' tumor: a Children's Cancer Group report.

BACKGROUND: The outcome of children with relapsed Wilms' tumor is poor, especially with poor-risk factors such as unfavorable histology, early recurrence, previous three-drug therapy, relapse not confined to lungs and abdominal relapse following abdominal radiotherapy. We report the overall response rate, progression-free survival and overall survival of 11 children with relapsed and poor-risk Wilms' tumor following ifosfamide/carboplatin/etoposide (ICE) chemotherapy. PATIENTS AND METHODS: ICE therapy consisted of ifosfamide 1800 mg/m2/day (on day 0-4), carboplatin 400 mg/m2/day (on day 0-1) and etoposide 100 mg/m2/day (on day 0-4). The median age at diagnosis was 39 months (range from 13 months to 16 years) and the median time to relapse after initial diagnosis was 9 months (range 4-72 months). All but one patient had at least one poor prognostic feature, with eight patients showing three or four. RESULTS: After ICE chemotherapy the number of patients showing a complete response (CR) was three (27%) and a partial response (PR) was six (55%). The overall response rate (CR+PR) was 82%. Five of the six patients with a PR subsequently achieved a CR with further therapy. The 3-year event-free survival and overall survival were 63.6 +/- 14.5%. CONCLUSIONS: The response rate in children with relapsed and poor-risk Wilms' tumor is >80% with ICE re-induction chemotherapy followed by post-ICE therapy. The optimal approach for post-ICE consolidation therapy has yet to be determined.     

Cytostatic therapy of advanced squamous cell carcinoma of the head and neck. A randomized study comparing cis-dichlorodiammineplatinum(II) and bleomycin with methotrexate and vindesine

79 patients were randomized and treated either with cis-DDP 33 mg/kg i.v. day 1 and BLM 15 mg/m2 i.v. continuously day 2-6 (arm A) or less aggressively with MTX 30 mg/m2 i.v. day 1 + 6 and VDS 3 mg/m2 day 2 + 7 (arm B). Patients with inadequate response were further treated with the alternative regimen ("cross over"). Regarding response rates therapy A was superior to B (p = 0.01) respectively p = 0.05 for the cross over patients. Not pretreated in comparison to pretreated patients demonstrated not significantly better results. Pretreated patients had statistically superior response rates with arm A than with arm B (p = 0.05). All other prognostic factors were without any influence on treatment results. CR induced by chemotherapy (2 X) in not pretreated patients could be increased by additional surgery and X-ray therapy (CR = 26X). Survival times demonstrated no difference between both regimes. Chemotherapy was of less influence on median survival times after 39 months than in comparison to post-chemotherapeutically performed surgery +/- radiotherapy in 44 not pretreated patients. Chemotherapy: CR + PR to MR + NC + PD 16 respectively 13 months with 38 respectively 48% survivors (p = 0.25). Surgery +/- radiotherapy: CR + PR median not reached yet, MR + NC + PD 13 months with 60 respectively 18% survivors (p = 0.001).     

Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas

We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.     

VIP (etoposide, ifosfamide, cisplatin) in adult patients with recurrent or refractory Ewing sarcoma family of tumors

Despite the fact that Ewing sarcoma family of tumors (ET) is chemosensitive, long-term survival is extremely rare for patients with primary refractory or recurrent disease. There is no standard salvage chemotherapy regimen available in this context. In this study the authors reviewed their experience with the combination of etoposide, ifosfamide, and cisplatin in adult patients with recurrent or refractory disease. From February 1997 through December 2001, they evaluated the efficacy of etoposide (75 mg/m2/day for 5 days), ifosfamide (1,200 mg/m2/day for 5 days), and cisplatin (20 mg/m2/day for 5 days) combination chemotherapy (VIP regimen), as second-line salvage therapy in 27 patients with recurrent or refractory ET. All patients were evaluated for response, time to progression, and overall survival. Twenty-one male and 6 female patients with recurrent (n = 14) and refractory (n = 13) disease were treated with the VIP regimen. Median age was 18 years (range, 16-34 years). Twenty-two patients were previously treated with vincristine, Adriamycin, ifosfamide, and actinomycin-D; and 5 patients were treated with cyclophosphamide, Adriamycin, and vincristine. Sites of recurrent or progressive disease included local (n = 3), distant (n = 11), and both local and distant (n = 13). A total of 129 cycles of VIP were given (median, 5 cycles/patient; range, 1-14 cycles/patient). One patient (4%) had a complete response (CR) and 8 patients (30%) had a partial response (PR), for an overall response rate of 34%. The median number of cycles given to patients with CR + PR was 6 (range, 3-14 cycles). Nine patients (33%) had stable disease and 9 (33%) had disease progression. Median time to progression and median overall survival were 6.6 months and 8.1 months respectively for all patients, and 12.8 months and 14.2 months respectively for responders. There were no toxic deaths. Major toxicities included grade IV granulocytopenia in 19 patients and grades III/IV thrombocytopenia in 15 patients. At a median follow-up of 8 months (range, 2-56 months), 24 patients died of disease progression, 2 patients are alive with disease, and 1 patient is alive with no evidence of disease. The authors conclude that the VIP combination is active in patients with recurrent/refractory ET, with acceptable toxicity, and offers good palliation. Cisplatin-based combination chemotherapy merits further investigation, possibly as first-line treatment in this disease.     

A phase II study of the combination of carboplatin and ifosfamide in previously untreated metastatic small cell lung carcinoma.

This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.     

培美曲塞联合顺铂一线治疗晚期非鳞状非小细胞肺癌的疗效观察

目的观察培美曲塞联合顺铂一线治疗晚期非鳞状非小细胞肺癌的疗效及不良反应。方法36例经组织学或细胞学确诊为非鳞状非小细胞肺癌而且未经化疗的晚期肺癌患者纳入本研究。化疗方案为：培美曲塞 500 mg/m2,静脉滴注,第一天;顺铂75 mg/m2,静脉滴注,第一天或分为第一至第三天。每21天为一周期,至少接受2周期化疗,但最多不超过6周期。所有患者进行疗效及不良反应评估。结果36例患者共化疗151周期,平均化疗周期数4.1。其中完全缓解（CR）0例,部分缓解（PR）17例,疾病稳定（SD）9例,疾病进展（PD）10例,有效率（CR+PR）为47.2%,疾病控制率（CR+PR+SD）为72.2%。中位无疾病进展生存时间为6.6月。主要不良反应为Ⅰ～Ⅱ度骨髓抑制,没有治疗相关性死亡。结论培美曲塞联合顺铂一线治疗晚期非鳞状非小细胞肺癌疗效较好而且不良反应轻。     

Cisplatin, epirubicin and 5-fluorouracil combination chemotherapy for recurrent carcinoma of the salivary gland

Nine patients (5 males, 4 females; median age, 62 years) with recurrent high-grade malignancies of major (7 cases) and minor (2 cases) salivary gland origin (4 adenoid cystic carcinomas, 2 adenocarcinomas, 2 poorly differentiated carcinomas, 1 mixed malignant tumor) were treated with cisplatin (60 mg/m2), epirubicin (50 mg/m2) and 5-fluorouracil (600 mg/m2) (CEF) by intravenous injections on the first day of a 21-day regimen. Previous therapy included surgery (1 case), radiotherapy (1 case), and surgery + radiotherapy (7 cases). There was 1 complete response (11.1%), 3 partial responses (33.3%), 2 unchanged lesions (22.2%) and 3 progressions (33.3%). Patients with local recurrence had a better response. Median remission duration was 7.5 months in CR + PR patients. Median overall survival was 8+ months; 14+ months for responders and 4 months for nonresponders. The major toxic effects were nausea/vomiting and alopecia; myelosuppression was less frequent and usually not severe.     

Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.     

伊立替康、顺铂、卡培他滨联合化疗治疗晚期食管癌的疗效观察

目的 观察伊立替康、顺铂、卡培他滨联合化疗对晚期食管癌的近期疗效及不良反应.方法 经临床明确诊断的晚期食管癌病人21例,接受伊立替康、顺铂、卡培他滨联合化疗,伊立替康180mg/m2,d1,顺铂20mg/m2,d1- d5,卡培他滨2000mg/(m2*d),分早、晚2次口服,d1- d14,3周为一周期,治疗两个周期评价疗效一次.结果 21例患者可评价客观疗效和不良反应.完全缓解(CR)1例,部分缓解(PR)9例,稳定(SD)4例,进展(PD)7例.客观效率(RR)47.6%,疾病控制率(DCR)66.7%,中位疾病进展时间(mTTP)5.8个月.主要不良反应为腹泻、中性粒细胞减少及恶心和呕吐.结论 伊立替康、顺铂、卡培他滨联合化疗对晚期食管癌的疗效较好,不良反应可以控制.     

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report

Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC).Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning.Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC.Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC.Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR >2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.     

顺氯氨铂、丝裂霉素和平阳霉素联合治疗食管癌41例结果

1986年7月～1987年12月采用顺氯氨铂、丝裂霉素、平阳霉素联合化疗治疗食管癌41例。完全缓解6例(14.6％),部分缓解17例(41.5％),微效9例(21.9％),稳定4例(9.8％),无效5例(12.2％)。完全缓解和部分缓解率(CR+PR)56.1％,总有效率(CR+PR+MR)78％,中位生存期7个月(2—32个月)。毒副反应有食欲减退,恶心、呕吐、脱发、发热、骨髓抑制.     

Combination chemotherapy of docetaxel, ifosfamide and cisplatin (DIP) in patients with metastatic urothelial cancer: a preliminary report

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of a new combination chemotherapy of docetaxel, ifosfamide and cisplatin (DIP) in the treatment of metastatic urothelial cancer. METHODS: Fourteen patients (nine male and five female; aged 59-82 years) with metastatic urothelial carcinoma, including five patients who have a history of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) chemotherapies, received the combination of docetaxel 60 mg/m(2) on day 1, and ifosfamide 1.0 g/m(2) and cisplatin 20 mg/m(2) on days 2-6 and repeated every 21 days, to a maximum of six cycles. Eligibility criteria included performance status (World Health Organization) 0-3; normal bone marrow and liver function; and no symptomatic peripheral neuropathy. RESULTS: Ten of the 14 patients (72%) demonstrated a partial response (PR), with durations of response ranging from 3 to 12 months [median 6.5 months; 95% confidence interval (CI), 4.1-8.7 months]. The response rate of the five patients with MVAC-refractory cancer was 80% with median duration of response 5.5 months, comparable with that of the cases without previous MVAC therapies. Grade 3-4 granulocytopenia occurred in 10 cases (71%), resulting in three episodes (21%) of febrile neutropenia. Grade 3 thrombocytopenia was observed in five cases (36%). No toxic death was observed. Grade 2 peripheral neuropathy was identified in one case. CONCLUSIONS: This pilot study demonstrated that DIP is an effective regimen for the treatment of metastatic urothelial cancer, and warrants further investigation.     

伊立替康联合顺铂治疗原发灶不明癌的临床观察

目的 评价伊立替康联合顺铂方案一线治疗原发灶不明癌的疗效及预后相关因素。方法 72例患者入组,2例患者未治疗,70例患者采用伊立替康联合顺铂方案,伊立替康180 mg/m2,静脉滴注,d1;顺铂75 mg/m2,静脉滴注d1~3,21天为一周期。结果 66例可评价疗效,其中4例CR,24例PR,16例SD,22例PD,ORR（CR+PR）为42.4%。中位至进展时间4.5月,中位生存期10.3月,1、2年生存率分别为38.9%和8.3%。最常见的不良反应包括中性粒细胞减少、恶心和呕吐。体能状况评分0-1、转移部位的数目＜3、局限于淋巴结的患者有更长的生存期（P＜0.05）。结论 伊立替康联合顺铂治疗原发灶不明癌安全而有效。体能状况、转移部位的数目、是否局限于淋巴结为原发灶不明癌的重要预后因素。     

Three conventional-drug combination (ifosfamide, carboplatin, etoposide--ICE regimen) in advanced non-small cell lung cancer (NSCLC)

Fifty consecutive patients with stage IIIB-IV non-small cell lung cancer (NSCLC) received the ICE regimen at intermediate doses (ifosfamide 1 g/m2, carboplatin 120 mg/m2, etoposide 80 mg/m2, day 1 to 3, q.4 weeks, for a maximum of 6 cycles). Overall 2 complete response (CR) and 10 partial response (PR) (overall response, OR: 24%, 95% C.I. 14-37%) were observed. An additional 7 patients had stable disease (SD) lasting more than 6 months, therefore a clinical benefit (CR+PR+SD >6 mos) was achieved in 19 patients (38%). Median time-to-progression (TTP) was 7 months and median overall survival (OS) was 11 months; 1- and 2-year survival rates were 36% and 10%. The ICE regimen was well tolerated and devoid of any cardiac, hepatic or neurologic toxicity. Moderate nausea and vomiting were easily manageable, grade 2 alopecia was universal, while hematological toxicity was mild (grade 2 leuko- and thrombocytopenia). Due to its efficacy and safety profile, this 3-drug regimen can be considered for routine community use.     

A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer.

A total of 92 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5) (PE) or cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5)/ifosfamide (2 g/m2, days 1, 2, 3) (PEI) combination chemotherapy. After 2 courses of chemotherapy, patients with limited disease (LD) received chest irradiation of 40-50 Gy. Of the 89 patients who could be wholly evaluated, the overall response rate was 78% for PE and 74% for PEI therapy (NS). For all patients the complete response (CR) rates were 14 versus 21%, respectively, and 22 versus 30% for LD. However, the median survival times for all patients were 55 weeks for PE therapy versus 56 weeks for PEI therapy (NS). The 2-year survival rates were 15 and 17%, respectively, for all patients (NS). There was no difference in the duration of response between PE and PEI therapy in cases with CR or partial response. However, severe leukopenia (< 2,000/mm3) occurred more often after PEI (73%) than after PE (44%) therapy (p < 0.05). These results suggest that PEI is not superior to PE chemotherapy in SCLC. The use of ifosfamide in multimodality treatment regimens needs to be studied further.     

Induction chemotherapy followed by concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer

The favourable experience with the combination regimen of vinorelbine, ifosfamide and cisplatin (NIP) in patients with metastatic non-small cell lung cancer (NSCLC) has led to a protocol assessing this regimen as an induction treatment in patients with stage III unresectable NSCLC, followed by thoracic radiotherapy with concurrent daily cisplatin as a radiosensitizer. Two cycles of NIP were administered 21 days apart; each cycle comprised i.v. vinorelbine 25 mg/m2 on days 1 and 8, i.v. ifosfamide 3 g/m2 on day 1 with MESNA as uroprotection, and i.v. cisplatin 50 mg/m2 on day 1. Radical thoracic radiotherapy commenced on day 43 to a total dose of 64 Gy and i.v. cisplatin 6 mg/m2 was given concurrently prior to each fraction of radiation as a sensitiser. Two more cycles of NIP were given to patients who responded favourably to the induction treatment about 2 weeks after completion of radiation. Between July 1995 and July 1997, 44 patients were treated with this protocol. This treatment schedule was generally well tolerated. Grade 3-4 neutropenia occurred in 50% of the patients and neutropenic sepsis was seen in 8. Grade 3-4 oesophagitis was uncommon. Most of the patients were able to complete the induction and concurrent chemoradiotherapy phase. Major response occurred in 75% of the patients with 2 (4.5%) complete responses (CR). A total of 6 patients achieved CR after chemoradiotherapy. At a median follow-up of 35 months, the median overall survival for all patients was 15 months with a 3-year survival rate of 24%. The median overall survival for stage IIIA patients was 19 months with a 3-year survival rate of 39% in contrast to 13 months' median overall survival and only 15% 3-year survival rate for stage IIIB. The NIP regimen results in a high response rate in NSCLC and this treatment programme seems to benefit selected patients with stage III disease.     

培美曲塞联合顺铂一线治疗晚期肺腺癌的临床观察

为了观察培美曲塞联合顺铂治疗晚期(ⅢB～Ⅳ)期肺腺癌的疗效及毒副反应,选取32例晚期肺腺癌患者,应用培美曲塞500 mg/m2,静脉滴入15 min,d;顺铂75 mg/m2,静脉滴入,d1(培美曲塞后),21 d为1个周期,至少2个周期评价疗效.32例患者均可评价疗效,CR1例,PR 10例,SD10例,PD11例,总有效率(CR+PR)为34.3％.所有患者中位疾病进展时间( TTP)为5.8个月(1.2～9.8个月),中位生存时间(OS)为12.1个月(3.8～26.5个月).主要毒副反应为胃肠道反应65.6％,多为Ⅰ～Ⅱ度;白细胞减少41.2％,多为Ⅰ～Ⅱ度.初步研究结果提示,培美曲塞联合顺铂治疗晚期肺腺癌疗效较好,不良反应小,安全性高.     

吉西他滨联合顺铂一线治疗晚期triple-negative乳腺癌41例临床研究

目的：观察吉西他滨联合顺铂（GP）一线治疗triple-negative（ER、PR、HER-2均阴性）晚期转移性乳腺癌的疾病进展时间、疗效和安全性。方法：2008年1月-2010年4月共41例经免疫组化检查证实为tri-ple-negative的晚期乳腺癌初治患者参与研究。患者接受吉西他滨联合顺铂方案治疗：吉西他滨1000mg/m2,静脉滴注30min,d1、d8;顺铂25mg/m2静脉滴注d1-3天,21天重复。结果：全组41例共完成160个周期的治疗,中位数4个周期,范围2-6个周期,均可评价疗效。完全缓解（CR）2例（4.88%）,部分缓解（PR）21例（51.22%）,病情稳定（SD）7例（17.07%）,病情进展（PD）11例（26.83%）。临床总缓解率（CR＋PR）56.10%;疾病控制率（CR＋PR＋SD）73.17%;中位疾病进展时间（mTTP）8.4个月,1年生存率65.85%。不良反应主要为Ⅰ-Ⅱ度骨髓抑制、末梢神经毒性、胃肠道反应、轻度肝功能损伤等。结论：吉西他滨联合顺铂一线治疗triple-negative晚期转移性乳腺癌患者,初步观察疗效较好,不良反应可耐受,值得进一步研究。     

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults.

PURPOSE: Patients with metastatic or locally advanced, unresectable soft tissue sarcoma (ASTS) are seldom curable, with 5-year survival rates of less than 10% in all large series. The role of high-dose chemotherapy (HDCT) with hematopoietic stem-cell support in this disease is not established. PATIENTS AND METHODS: Between 1988 and 1994, 30 patients with ASTS who responded to a standard chemotherapy regimen were included in a prospective pilot study of HDCT as consolidation therapy using ifosfamide (12 g/m(2)), etoposide (800 mg/m(2)), and cisplatin (200 mg/m(2)) (VIC). RESULTS: The median duration of grade 4 neutropenia and thrombocytopenia was 14 and 10 days, respectively. Nineteen patients (63%) experienced grade 1 or higher renal toxicity. All eight patients in complete remission (CR) before HDCT were still in CR at day 60. Of the 22 patients in partial remission (PR) or with a minor response to conventional chemotherapy, CR, PR, and stable disease were achieved in four (18%), three (13%), and 12 patients (54%), respectively, by day 60, while three patients (14%) progressed. With a median follow-up of 94 months, overall and progression-free survival rates at 5 years after HDCT were 23% and 21%, respectively. Patients in CR before HDCT had a significantly superior 5-year overall survival rate compared with other patients (75% v 5%; P: =.001). CONCLUSION: Despite the toxicity of the VIC regimen, a high survival rate was observed in HDCT-treated patients who were in CR after conventional chemotherapy. A phase III randomized trial is required to establish the role of HDCT in ASTS.     

Results of 2 multicenter therapy studies in inoperable non-small cell bronchial cancer

A total of 166 patients with non-small cell lung cancer (NSCLC) were included in two multicenter trials testing different treatment regimens. In study I, 116 patients received 4 cycles of aggressive polychemotherapy consisting of cis-platinum 100 mg/m2 (day 1), etoposide 100 mg/m2 (days 4-6), and vindesine 3 mg/m2 (day 1) (CEV); patients without distant metastases subsequently received chest irradiation with 50 Gy. In study II, 50 patients were treated with monochemotherapy consisting of etoposide 250 mg/m2 (days 1-3), and ifosfamide 5 g/m2 as 24-h infusion (day 29). While this program was repeated in responders with extensive disease (ED), patients with limited disease (LD) subsequently received chest irradiation with 50 Gy using 20 mg/m2 cis-platinum weekly as a radiosensitizer. Response rates (CR + PR) to chemotherapy were higher in study I than in study II, and were 26% (CR 3%) vs. 8% (CR 0%) for all patients, 18% (CR 0%) vs. 4% (CR 0%) for ED, and 45% (CR 11%) vs. 13% (CR 0%) for LD. The increase in response rates by radiotherapy was marginal in study I (CR + PR 47%, CR 18%), but remarkable in study II (CR + PR 42%, CR 29%). While median survival was slightly longer in study I than in study II for ED (7.7 vs. 6.6 months) and LD (14.4 vs. 12.0 months), the 2-year survival rate was in favor of study II (10% vs. 25%). Toxicity was clearly more pronounced in study I, including 3 lethal complications and 16 discontinuations of therapy due to side effects or refusal. Thus, while in ED the efficacy of both treatment regimens was very restricted, in LD radiotherapy with cis-platinum as a radiosensitizer achieved a relatively high 2-year survival rate which justifies further testing of this treatment strategy.