A Phase II Study of the Docetaxel–Carboplatin Chemotherapy Regimen in Advanced Non-Small-Cell Lung Cancer

The efficacy of the docetaxel–carboplatin combination chemotherapy was studied in various phase II studies. Based on these data we aimed to test the regimen in previously untreated patients with advanced advanced non-smoking lung cancer (NSCLC) with docetaxel 80 mg/m² a standard dose of carboplatin at AUC = 5, in an attempt to define the efficacy and tolerability of the combination in an open-label phase II study. Patients with histologically confirmed advanced NSCLC stage IIIB and IV were candidates for the present study. Docetaxel was administered at 80 mg/m² over 1 h by intravenous (IV) infusion followed by carboplatin AUC = 5 in 30 min IV infusion, both on day 1, and recycled every 21 days. Sixty patients received 263 courses of therapy in total; 231/263 (88%) were administered according to the planned doses, and 48/60 (80%) patients received chemotherapy without decrement of the dose; 32/263 (12%) of the courses were administered with a 10%–30% dose reduction. Complete responses (CR) were seen in 5 patients (8.3%) and partial responses (PR) in 16 patients (26.7%) for an overall response rate of 35%. Median duration of response was 7.5 months [95% confidence interval (CI)-7.1–7.9], time to progression (TIP) 11.5 months (95% CI-8.2–14.8), median overall survival (OS) 15.0 months (95% CI-10.8–19.2). One-year survival was 61.7%. Toxicity was acceptable; it was calculated according to the administered cycles and was mainly neutropenia: grade 3, 9% and grade 4, 2%; anemia: grade 3, 8%; nausea and vomiting: grade 3, 8%. The outpatient regimen of docetaxel–carboplatin is effective with acceptable toxicity in patients with advanced NSCLC.     

Combination chemotherapy with carboplatin and docetaxel for elderly patients with non-small-cell lung cancer

The efficacy and toxicity of treatment with carboplatin (AUC= 5)+ docetaxel (70mg/m2) were analyzed retrospectively in 27 elderly patients with advanced non-small-cell lung cancer (NSCLC) aged 70 years or more. The median age of the patients was 74 years (range, 70-83 years). The performance status (ECOG), clinical stage, and tumor histology in the patients were as follows: PS: PS 0, 12 patients; PS 1, 11 patients; PS 2, 4 patients; disease stage: stage IIIA, 5 patients; stage IIIB, 11 patients; stage IV, 11 patients; tumor histology: adenocarcinoma, 18 patients; squamous cell carcinoma, 9 patients. The median number of treatment cycles administered was 4. The median survival time was 11.1 months and the 1-year survival rate was 40.7%. The response rate was 33.3%. The major toxicities were leukopenia and neutropenia; grade 3/4 neutropenia occurred in 22 patients (81.5%). Nonhematologic toxicities were generally mild, including grade 3 anorexia in 13 patients (48.1%) and grade 3 febrile neutropenia in 9 patients (33.3%). No treatment-related deaths were observed. Thus, it was concluded that the combination of carboplatin + docetaxel is a feasible, well-tolerated, and effective regimen for fit elderly patients with NSCLC. Prospective studies comparing carboplatin + docetaxel with third-generation single-agent chemotherapy or non-platinum-based combination chemotherapy are needed to confirm the efficacy and safety of this drug combination.     

多西他赛联合卡铂治疗老年晚期非小细胞肺癌临床观察

目的观察多西他赛（docetaxel）联合卡铂（carboplatin）治疗老年晚期非小细胞肺癌的临床疗效及毒副反应。方法老年晚期非小细胞肺癌患者共40例,多西他赛用量75mg/m^2,每天静脉滴注,同时配伍卡铂AUC=5mg·ml^-1·min^-1,每天静脉滴注。21～28d为1个疗程,每例患者至少接受2个疗程的治疗。结果40例患者均可评价疗效,无完全缓解病例（CR）,15例获部分缓解（PR）,20例稳定（SD）,5例疾病进展（PD）,总有效率为37．5％（15／40）,其中位疾病进展时间为4．5个月,中位生存时间10．2个月（3～20个月）,1年生存率为45．1％。毒性反应主要有骨髓抑制、恶心、呕吐和腹泻以及白细胞下降导致的发热等。但患者多为Ⅰ、Ⅱ度反应,耐受良好。结论多西他赛联合卡铂是一种对老年晚期非小细胞癌有效的治疗方法,毒性反应轻,临床使用安全。     

Epirubicin, cyclophosphamide and weekly paclitaxel as neoadjuvant chemotherapy for stage II and III breast cancer

Purpose: To assess the efficacy and the toxicity of a new combination of epirubicin, cyclophosphamide and paclitaxel as neoadjuvant chemotherapy for breast cancer. Methods: Patients with stage II and III breast cancer received 3–4 cycles of epirubicin 75 mg/m² plus cyclophosphamide 600 mg/m² on day 1, and paclitaxel at a dose of 100 mg on days 1, 8, 15 and 22 on a 28-day cycle. Results: Forty-nine patients were enrolled in the study. Stage II was present in 16 patients (32.7%) and stage III in 33 patients (67.3%). Relevant toxicities were nausea/vomiting grades III–IV in 6 patients (12.2%) and neutropenia grade III–IV in 33 patients (67.3%). The overall clinical response rate was 83.7%. Partial response was observed in 25 patients (51%), complete response in 16 patients (32.7%), stable disease in 7 patients (14.3%) and progression in 1 patient. Thirty-three non-inflammatory breast cancer patients underwent surgery, 29 with breast-conserving surgery (87.9%). Pathological complete response was found in 5 patients (15.1%). Conclusions: The combination of epirubicin, cyclophosphamide and weekly paclitaxel as given in this study is safe and shows good activity in the neoadjuvant setting of stage II and III breast cancer patients.     

A study of weekly docetaxel and carboplatin as first-line chemotherapy for advanced non-small cell lung cancer

Background

Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC).

Methods

Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m² on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles).

Results

Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively.

Conclusions

The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.     

Complete regression of advanced esophageal cancer with abdominal bulky lymph node metastasis treated by concurrent chemoradiotherapy using docetaxel, cisplatin, and 5-fluorouracil

In an attempt to improve survival of patients with locally advanced esophageal cancer, chemoradiotherapy consisting of cisplatin, 5-fluorouracil (5-FU), and irradiation has recently been used. For such patients, concurrent chemoradiotherapy using docetaxel in combination with cisplatin and 5-FU has been introduced and is under evaluation. We herein report an esophageal cancer patient with concomitant distant lymph node metastasis in whom a complete response was achieved by chemoradiation therapy. A 46-year-old man was diagnosed as having stage IV A esophageal cancer with synchronous bulky metastasis in the celiac lymph node, and concurrent chemoradiotherapy was started. Chemotherapy consisting of docetaxel (30 mg/m² on days 1, 8), cisplatin (60 mg/m² on day 1), and 5-FU (200 mg/m²/day, continuous infusion on days 1–14) was performed for 2 cycles. At the same time, irradiation therapy (1.8 Gy/day on 1–5 days every week for 6 weeks) was employed for both local and metastatic lesions. Although the patient experienced severe hematological toxicity throughout the course, chemoradiotherapy resulted in complete regression of both local and metastatic disease. Subsequently, he was followed as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the combination therapy. Thus, concurrent chemoradiotherapy may be effective for esophageal cancer, even with visceral metastasis.     

培美曲塞联合卡铂治疗老年晚期非小细胞肺癌临床观察

目的观察培美曲塞（pemetrexed）联合卡铂（carboplatin）治疗老年晚期非小细胞肺癌的临床疗效及毒副反应。方法老年晚期非小细胞肺癌患者共46例,培美用量75ms／m^2,每天静脉滴注,同时配伍卡铂AUC=5mg·ml^-1·min^-1,每天静脉滴注。21天为1个疗程,每例患者至少接受2个疗程的治疗。结果46例患者均可评价疗效,无完全缓解病例（CR）,21例获部分缓解（PR）,20例稳定（SD）,5例疾病进展（PD）,总有效率为45．6％（21／46）,其中位疾病进展时间为4．7个月。中位生存时间10．3个月（3-20个月）,1年生存率为52．2％。毒性反应主要有骨髓抑制、恶心、呕吐和腹泻以及白细胞下降导致的发热等。但患者多为Ⅰ、Ⅱ度反应,耐受良好。结论培美曲塞联合卡铂是一种对老年晚期非小细胞癌有效的治疗方法,毒性反应轻,临床使用安全。     

VATS lobectomy facilitates the delivery of adjuvant docetaxel-carboplatin chemotherapy in patients with non-small cell lung cancer

Background

To evaluate the safety and tolerability of docetaxel/carboplatin regimen in the post-operative setting of patients with non-small cell lung cancer (NSCLC).

Methods

Enrolment of 133 patients with stage Ib - IIIa NSCLC was undertaken in an open-label, single arm study to assess the safety and tolerability of docetaxel (75 mg/kg) and carboplatin (AUC 5.5) administered for 3 cycles after resection for curative intent. The primary endpoint of the study was safety, as reflected by a febrile neutropenia rate of <10%. Other endpoints assessed protocol compliance and the impact of minimally invasive surgical technique.

Results

Patient accrual was completed at 1 center in the US and 10 centers in China in <6 months. Febrile neutropenia complicated treatment in 12 patients (9.0%), below the predetermined safety threshold of 14 patients. Four VATS and 8 open thoracotomy patients experienced febrile neutropenia (P=0.26). Completion of the three-cycle adjuvant regimen was achieved in 86% (95% CI, 77-95%) of patients. Sixty-two of 66 VATS patients compared to 53 of 67 open thoracotomy patients received all three doses according to protocol (P<0.01). Thirteen serious adverse events (9.8%) and no deaths were attributed to the study regimen.

Conclusions

In this rapidly accrued study, docetaxel and carboplatin were well-tolerated in the adjuvant treatment of NSCLC. Adjuvant treatment compliance was higher among patients undergoing a minimally invasive surgical approach. (ClinicalTrials.gov number {"type":"clinical-trial","attrs":{"text":"NCT00883675","term_id":"NCT00883675"}}NCT00883675).KEYWORDS : Non-small cell lung cancer, adjuvant chemotherapy, docetaxel, carboplatin     

A phase I study of combination therapy with S-1 and irinotecan (CPT-11) in patients with advanced colorectal cancer

Purpose  The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer. Methods  S-1 was administered orally at 80 mg/m² per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m² per day, stepping up to 100, 120 or 150 mg/m² per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed. Results  A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m², because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m². Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0–14.0 months). Conclusion  A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.     

A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaïve patients with metastatic or locally advanced non-small cell lung cancer

AIMS: To evaluate the efficacy and safety of docetaxel-cisplatin in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). METHODS: Chemotherapy-na?ve patients with histologically confirmed TNM stage III or IV NSCLC were recruited from 12 Asian trial centers. Patients received docetaxel (75 mg/m2) and cisplatin (75 mg/m2) every 3 weeks for 6 cycles. RESULTS: 130 of 146 patients were evaluable for efficacy (60% stage IV). Three complete and 58 partial responses were observed (overall response rate: 46.9%; 95% CI: 38.3-55.5%). Median time to progression was 6.9 months and median survival was 14.0 months; 1-year survival was 59.5%. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 69.2%, 6.2% and 18.5% of patients, respectively. Grade 3/4 vomiting was observed in 13.7% and grade 3/4 neurosensory effects were observed in 2.7% of patients. There was one case of treatment-related death due to sepsis. CONCLUSION: Docetaxel-cisplatin is an effective and well-tolerated treatment in Asian patients with NSCLC.     

多西紫杉醇联合卡铂治疗晚期非小细胞肺癌的疗效观察

目的观察多西紫杉醇联合卡铂治疗晚期非小细胞肺癌近期疗效及毒副反应。方法47例晚期非小细胞肺癌住院患者给予多西紫杉醇联合卡铂治疗,多西紫杉醇75mg/m2,静滴,d1,卡铂根据AUC5计算用量,静滴,d1,21d为1周期,每个患者均完成2个周期以上,评价疗效和不良反应,并随访生存期。结果47例患者治疗后CR0例、PR24例、NC17例、PD6例,有效率为51.1%。KS评分增加者70.2%(33/47)、稳定21.3%(10/47)、下降8.5%(4/47)。中位生存期9个月(95%CI8～10个月),1年生存率27.1%。最常见的毒副反应为骨髓抑制,全组68.1%(32/47)出现白细胞下降,其中Ⅲ度～Ⅳ度白细胞减少发生率为25.5%,恶心、呕吐29.8%(14/47),脱发87.2%(41/47)。其余毒副反应轻微,均可耐受。结论多西紫杉醇联合卡铂治疗晚期非小细胞肺癌有较好的疗效,毒副反应比较轻微。     

Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non–small lung cancer with EGFR TKIs-resistant mutation

Purpose  

Previous studies have demonstrated that sunitinib has the anti-tumor activity in human non–small cell lung cancer (NSCLC). This study was aimed to investigate the efficacy of single use of sunitinib and that of concurrent or sequential administration of sunitinib and docetaxel in NSCLC cell lines that are resistant to EGFR TKIs.     

Carboplatin plus paclitaxel in the treatment of advanced or recurrent endometrial carcinoma

Purpose To evaluate the efficacy and safety of the combination of carboplatin plus paclitaxel in patients with advanced, metastatic and recurrent endometrial cancer. Methods Medical records were retrospectively reviewed to identify endometrial cancer patients treated in the Gynecologic Cancer Program of the Cleveland Clinic with carboplatin/paclitaxel who had both a histologic diagnosis of endometrial adenocarcinoma and either measurable (CT scan, physical examination) or evaluable (CA-125 criteria) disease. Results From 1994 to 2003, 22 individuals (median age 65 years) meeting the above noted criteria received a total of 23 courses of carboplatin (AUC 4–6)/paclitaxel (135–175 mg/m2) administered on a 21-day schedule (median six cycles/patient). The overall response rate was 87% (20/23). The most common toxicity was hematologic. Five patients required dose reductions due to excessive toxicity (three hematologic, one gastrointestinal, one fatigue). There were no treatment related deaths. With a median follow-up of 42 months, 13 patients have died of progressive cancer, while four currently have no evidence of disease at the time of last follow-up. Conclusions The combination of carboplatin plus paclitaxel demonstrates substantial biological activity in endometrial adenocarcinoma. The safety and efficacy of this regimen makes it an attractive option for first-line chemotherapy in patients with advanced or recurrent endometrial carcinoma.     

A phase II trial of docetaxel (Taxotere<Superscript>®</Superscript>) as second-line chemotherapy in patients with metastatic breast cancer

The efficacy and tolerability of docetaxel 100 mg/m2 every 3 weeks as second-line chemotherapy in patients with metastatic breast cancer was investigated. In addition, the efficacy of a 3-day prophylaxis against cumulative dose-related fluid retention was examined with methylprednisolone 32 mg twice daily for 3 days starting 12 and 3 h before the docetaxel infusion together with oral cetirizine 10 mg 12 and 3 h before start of docetaxel for prevention of acute hypersensitivity reactions. According to the intent to treat-analysis 35% (95%CI: 25; 46) of the 94 patients entered responded to therapy. Their median survival was 12 months (range 0–20 months). The respective response rate for the 87 patients eligible for response evaluation was 37% (95%CI: 27; 48). Their median duration of response was 8 months (range 3–12 months), their median time to progression was 4 months (range 1–12 months). The corresponding response rate in the eligible patient cohort with anthracycline-resistant disease was 28% (95%CI: 15; 45) and increased to 44% (95%CI: 30; 59) in the cohort with non-anthracycline-resistant disease. Patients with visceral metastases responded in 36% and patients with ≥3 organs involved in 33%. In a retrospective analysis, the 3-day premedication of corticosteroids and antihistamines proved to be as effective as the established but more toxic 5-day regimen in delaying and preventing the occurrence of docetaxel derived toxicities especially the cumulative fluid retention. In conclusion, docetaxel represents one of the most active agents for second-line treatment of metastatic breast cancer, especially for anthracycline-resistant patients. Due to comparable effectiveness of the 5-day regimen which is widely used by others and the 3-day premedication tested in this trial the latter proved to be more favourable and was therefore recommended for future therapies.     

Phase II trial of ifosfamide and cisplatinum in advanced ovarian cancer

To evaluate the efficacy of systemic ifosfamide, cisplatin (CDDP) combination as first line treatment followed by intraperitoneal (IP) chemotherapy with carboplatin (CBCDA) and etoposide as consolidation in patients with stage III and IV epithelial ovarian cancer. A total of 40 patients with stage III and IV ovarian cancer were entered into the study. Ifosfamide 1 glm² plus mesna 1 glm² was given as six hour infusion daily for six days and CDDP 75 mglm² was given on day seven. Patients completing six cycles of systemic therapy underwent second look laparotomy followed by four cycles of IP chemotherapy with CBCDA 300 mglm² and etoposide 200 mglm². Of the 40 patients entering the protocol 27 patients completed six cycles with a complete remission (CR) of 65% and overall response of 67.5%. Twenty-two patients underwent second look laparotomy with pathological CR in ten patients, microscopic disease in seven and macroscopic disease in five. Eleven patients completed four cycles of IP chemotherapy. At 52 months the overall survival (OS) was 36%. The disease free survival (DFS) at 45 months was 38%. Factors affecting OS were ascites (p<0.011), stage (p<0.04), weight change (p<0.017), residual disease (p<0.001), number of chemotherapy cycles (p<0.0001) and IP chemotherapy (p<0.006). Presently 35% patients are alive in CR, 15% are alive with disease, one patient has been lost to follow up while 47.5% have died. Of these four patients had progressive disease, seven relapsed, four died due to treatment related complications and two died in CR due to other causes. Subset analysis of 22 patients who had second look laparotomy and completed four cycles of IP chemotherapy revealed a distinct survival advantage. IFOS+CDDP is an effective combination as first time treatment in advanced ovarian cancer. IP chemotherapy is effective as consolidation and seems to provide a significant survival advantage. Further studies with larger number of patients need to be done to confirm these results.     

吉西他滨联合多西他赛治疗肺癌的临床观察

目的 探讨吉西他滨联合多西他赛治疗肺癌的临床疗效.方法 随机将我院收治的90例肺癌患者分为对照组60例与研究组30例.两组分别选用吉西他滨联合多西他赛的不同给药方案进行治疗.结果 两组患者的总缓解率比较无显著性差异（P＞0.05）.研究组中性粒细胞减少Ⅲ＋Ⅳ发生率明显低于对照组（P〈0.05）,两组间其他不良反应比较均无显著性差异（P＆gt;0.05）.结论 吉西他滨联合多西他赛治疗肺癌具有显著疗效,且多西他赛联合顺铂每周给药方案的安全性优于三周治疗方案.     

Phase II study of amrubicin combined with carboplatin for refractory relapsed small-cell lung cancer: North Japan Lung Cancer Group Trial 0802

BackgroundAmrubicin (AMR), a new anthracycline agent, has shown promising results for advanced small-cell lung cancer (SCLC), although the efficacy of AMR alone against refractory relapsed SCLC is insufficient. This study was conducted to evaluate the safety and efficacy of the combination of AMR and carboplatin (CBDCA) in patients with refractory relapsed SCLC.MethodsPatients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30 mg/m², days 1–3) and CBDCA (area under the curve 4.0 mg mL⁻¹ min⁻¹, day 1) every 3 weeks. The primary endpoint of this study was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival, and the toxicity profile. Assuming that an ORR of 45% in eligible patients would indicate potential usefulness and an ORR of 20% would be the lower limit of interest, with α=0.10 and β=0.10, at least 24 patients were required.ResultsAmong 29 eligible patients, the ORR was 34% (90% confidence interval, 20–48). The median PFS was 3.5 months, whereas the median survival time was 7.3 months. The most common grade 3–4 toxicity was neutropenia (79%), although only one patient (3%) suffered from febrile neutropenia. Non-hematological toxicities were of moderate severity and no treatment-related death was observed.ConclusionsThis is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. However, further investigation of this regimen is warranted.     

Long-term results of concurrent chemoradiotherapy followed by high dose rate brachytherapy for T2-3 N0-1 M0 esophageal carcinoma

Background To assess the long-term efficacy and the pattern of failure of concurrent chemoradiotherapy followed by high dose rate (HDR) brachytherapy for stage T2-3 N0-1 M0 esophageal carcinoma. Methods Forty-six patients with clinical stage T2-3 N0-1 M0 esophageal cancer received concurrent chemoradiotherapy followed by HDR brachytherapy. The chemotherapy regimen was a combination of cisplatin 60 mg/m² on day 1 and fluorouracil 600 mg/m² continuous infusion from days 1 to 4 during the first and last week of external-beam irradiation. Radiotherapy consisted of external beam to a total dose of 40–60 Gy (median, 50 Gy) and high dose rate brachytherapy to 8–24 Gy (median, 16 Gy) in 2–4 fractions. External beam was delivered to a field of the primary lesion and the involved nodal lesions. All patients were followed up for at least 5 years. Results The 5-year overall survival rate was 28%. The median survival duration was 22 months. The 5-year cause-specific survival rate was 34% and the median was 22 months. Persistent disease was found in 7 of 46 patients (15%). Of the 39 patients with initial complete tumor disappearance, locoregional failure occurred ultimately in 13 patients. The ultimate local control rate was 57% (26/46). Three patients were salvaged successfully with surgery. Four patients (9%) had regional recurrence out of the irradiated fields as first failure site. Four patients (9%) had recurrence 3 years or longer after treatment. Twelve patients had transient ulcers, which healed spontaneously within a few months. Massive esophageal bleeding, thought to be treatment related, occurred in 2 patients, leading to death. Severe late toxicity with esophageal ulceration was found in patients receiving a dose of 16–24 Gy via brachytherapy. Conclusions Concurrent chemoradiotherapy followed by HDR brachytherapy achieved long-term effective and curative results for stage T2-3 N0-1 M0 esophageal carcinoma. However, severe late toxicity was observed with 16–24 Gy via brachytherapy. We recommend a dose via HDR brachytherapy should be 12 Gy or less following concurrent chemoradiotherapy.     

Markov-modeling for the administration of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-line chemotherapy with epithelial ovarian carcinoma

Purpose So far there is no analysis available on the cost effectiveness of the paclitaxel/platinum-analogue combination versus carboplatin monotherapy with ovarian cancer. Up-to-now only a cost-utility analysis on ovarian carcinoma has been published (Ortega et al. in Gynecol Oncol 66(3):454–463, 1997), which in addition to the first-line chemotherapy included second-line chemotherapy with effectiveness and cost data in the analysis. Therefore, within the scope of our study the cost effectiveness of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-lie chemotherapy was to be determined with epithelial ovarian carcinoma. Methods For this purpose a decision-making Markov model was developed which represents the medical and economic consequences of the administration of paclitaxel and platinum derivatives in first-line chemotherapy and the administration of topotecan and liposomal doxorubicin in second-line chemotherapy in the treatment of epithelial ovarian carcinoma by means of data from the literature. Patients were treated either in the early (FIGO stage I–IIa) or advanced stage (FIGO stage IIb–IV). Results The therapeutic strategy caboplatin followed by topotecan costs 20,123.91 €, the therapeutic strategy carboplatin followed by liposomal doxorubicin 22,336.57 €, the therapeutic strategy carboplatin/pactlitaxel followed by liposomal topotecan 29,820.64 € and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin 31,560.47 € from the time of diagnosis until death or survival within 5 years. With lives saved, accordingly of 2.55, 2.70, 2.60 and 2.65 years’ costs amounted to 7,891 €, 8,270.35 €, and 11,453.62 € per year of life saved. Conclusions Based on the threshold value of social willingness to pay 45,500 € per year of life saved, the therapeutic strategy carboplatin followed by topotecan, the therapeutic strategy carboplatin followed by liposomal doxorubicin, the therapeutic strategy carboplatin/paclitaxel followed by topotcan and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin can be evaluated to be cost effective.     

Bendamustine as salvage treatment in patients with advanced progressive breast cancer: a phase II study

A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m² bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1–14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials. Received: 9 April 1998 / Accepted: 24 June 1998