Cost‐effectiveness of aprepitant in Japanese patients treated with cisplatin‐containing highly emetogenic chemotherapy

Chemotherapy‐induced nausea and vomiting (CINV) remains a major adverse event in cancer chemotherapy. Although aprepitant is effective in preventing CINV, an increment in financial burden for uniform use of aprepitant is a concern. The aim of the present study was to define the cost‐effectiveness of aprepitant from the perspective of the Japanese National Health Insurance system. Based on the results of a randomized phase II trial comparing an aprepitant‐containing regimen versus a nonaprepitant regimen in Japanese patients who received cisplatin‐containing highly emetogenic chemotherapy, a decision analytic model was developed. The incremental cost‐effectiveness ratio (ICER) was calculated both in the outpatient care setting (OCS) and in the inpatient care setting (ICS). The use of the aprepitant‐containing regimen was associated with improved quality of life compared with the nonaprepitant regimen, with an increment in quality‐adjusted life years (QALY) of 0.0016. The incremental total medical costs associated with the use of the aprepitant regimen were lower in the OCS than in the ICS, 6192 JPY (56.92 USD) and 9820 JPY (90.27 USD), respectively. The ICER was calculated as 3 906 698 JPY (35 910 USD) per QALY gained in the OCS and 6 195 781 JPY (56 952 USD) per QALY gained in the ICS. Cost‐effectiveness of the aprepitant‐containing antiemetic therapy was limited to the OCS, considering the threshold of willingness‐to‐pay commonly accepted (5 million JPY [45 960 USD] in Japan and 50 000 USD in the USA). The efficacy of aprepitant offsets the costs for revisiting clinics or rehospitalization added with rescue medications in the OCS.     

Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer.

The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m(-2) by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m(-2) by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m(-2) + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian approximately Pound 0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76,370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138,578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30,619 per LYG. When compared with historical controls treated with best supportive care, this regimen of paclitaxel/cisplatin cost $4539 per LYG. Assuming a 3-h paclitaxel infusion yields the same survival advantage as the 24-h infusion did in the randomized trial, paclitaxel/cisplatin is a cost-effective improvement over standard etoposide/cisplatin for patients with advanced non-small cell lung cancer.     

Economic analysis of vinorelbine plus cisplatin versus paclitaxel plus carboplatin for advanced non-small-cell lung cancer

BACKGROUND: It is increasingly important to have timely information about the economic impact of new cancer therapies in today's cost-conscious environment. Nearly 170 000 people are diagnosed with lung cancer annually in the United States. We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer. There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms. METHODS: Use of both protocol and nonprotocol lung cancer-related health care was tracked for 24 months from the initiation of therapy. To determine expenditures, nationally standardized costs were applied to each type of health care service used, and these were summed over time. Lifetime expenditures and 95% confidence intervals (CIs) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring. Student's t tests were used to compare the difference in costs between the arms. All statistical tests were two-sided. RESULTS: Cancer-related health care costs over the period of observation averaged 40,292 dollars (95% CI = 36,226 dollars to 44,359 dollars) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars (95% CI = 44,674 dollars to 53,208 dollars) for patients in the carboplatin plus paclitaxel arm (P =.004), with a mean difference of 8648 dollars (95% CI = 2634 dollars to 14,662 dollars). Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm (P =.0003 and P<.0001, respectively), whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm (P<.0001). There was no difference between the arms in costs for blood products, supportive care medications, nonprotocol-related inpatient or outpatient care, and nonprotocol chemotherapy. CONCLUSIONS: Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine. The majority of the cost difference is due to the additional cost of the protocol chemotherapy (approximately 12,000 dollars). Notable differences in costs of downstream health care were not apparent.     

Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. PATIENTS AND METHODS: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). RESULTS: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). CONCLUSION: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.     

Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study.

BACKGROUND: We compared the combination plus Carboplatin plus paclitaxel, which is considered the treatment of choice for initial chemotherapy of advanced ovarian cancer (AOC) with a regimen combining alternating carboplatin and cisplatin plus paclitaxel. The two platinum derivatives have been previously combined as they are not totally cross-resistant and as they share no overlapping toxicities. PATIENTS AND METHODS: Patients with AOC, after the initial cytoreductive surgery were randomized to either 6 courses of paclitaxel at 175 mg/m2 as 3 h infusion plus Carboplatin at 7 AUC (Arm A) or Paclitaxel at the same dose plus Carboplatin again at 7 AUC for cycles 1,3,5, while for cycles 2,4,6 Cisplatin at 75 mg/m2 substituted for Carboplatin (Arm B). RESULTS: 247 patients are analyzed. Significant differences were not found, both in terms of PFS (38 vs 39 months, p=0.95) and overall survival (40.6 vs 38.6 months, p=0.79). There was not also difference in 5-year survival rate (35% vs 39%) or 5-year PFS rate (23% vs 28%). Age >60, PS 2, stage IV disease and presence of residual disease were adversely related to the overall survival. CONCLUSION: Both regimens are well tolerated and effective. Alternating cisplatin with carboplatin does not improve the results compared with the standard combination.     

Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of platinum-sensitive, recurrent ovarian cancer

BACKGROUND:

In a randomized controlled trial (RCT) of patients with recurrent, platinum‐sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression‐free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single‐agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost‐utility model to compare these 2 regimens with the incorporation of prospectively collected quality‐of‐life (QoL) data.

METHODS:

An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy‐General questionnaire were converted to utilities. Costs and incremental cost‐effectiveness ratios (ICERs) were reported in US dollars per quality‐adjusted life year (QALY). Extensive 1‐way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed.

RESULTS:

The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost‐effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness‐to‐pay threshold, cDC was either dominant or cost‐effective with an ICER <$50,000 per QALY in 83% of simulations.

CONCLUSIONS:

Combined weekly cDC appeared to be cost‐effective compared with sDC as treatment strategy for patients with platinum‐sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment. Cancer 2011;. © 2011 American Cancer Society.     

Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial.

PURPOSE: Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non-small-cell lung cancer (NSCLC). To determine whether a new agent, paclitaxel, would further improve survival in NSCLC, the Eastern Cooperative Oncology Group conducted a randomized trial comparing paclitaxel plus cisplatin to a standard chemotherapy regimen consisting of cisplatin and etoposide. PATIENTS AND METHODS: The study was carried out by a multi-institutional cooperative group in chemotherapy-naive stage IIIB to IV NSCLC patients randomized to receive paclitaxel plus cisplatin or etoposide plus cisplatin. Paclitaxel was administered at two different dose levels (135 mg/m(2) and 250 mg/m(2)), and etoposide was given at a dose of 100 mg/m(2) daily on days 1 to 3. Each regimen was repeated every 21 days and each included cisplatin (75 mg/m(2)). RESULTS: The characteristics of the 599 patients were well-balanced across the three treatment groups. Superior survival was observed with the combined paclitaxel regimens (median survival time, 9.9 months; 1-year survival rate, 38.9%) compared with etoposide plus cisplatin (median survival time, 7.6 months; 1-year survival rate, 31.8%; P =. 048). Comparing survival for the two dose levels of paclitaxel revealed no significant difference. The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients (P =.152). For the stage IV subgroup, the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel (P =.246). With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias, neurotoxicity, and, possibly, increased treatment-related cardiac events with high-dose paclitaxel, toxicity was similar across all three arms. Quality of life (QOL) declined significantly over the 6 months. However, QOL scores were not significantly different among the regimens. CONCLUSION: As a result of these observations, paclitaxel (135 mg/m(2)) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial.     

EP方案与PC方案治疗进展期非小细胞肺癌的对比研究

目的:比较EP方案与PC方案治疗进展期非小细胞肺癌的疗效和毒性反应。方法:93例进展期非小细胞肺癌,分为EP方案组应用足叶乙甙加顺铂静脉滴注,PC方案组应用紫杉醇加卡铂静脉滴注,21天为1个周期,4个周期后评价疗效。结果:EP组45例,有效率14/45(31.1%),PC组48例,缓解率17/48(35.4%),中位生存时间(MST)EP组9.1个月,PC组8.9个月,1年生存率EP组34.3%,PC组30.8%,经统计学检验差异均无显著性(P>0.05)。骨髓抑制及消化道症状主要为毒性反应,差异无显著(P>0.05)。结论:EP方案与PC方案相比生存率无差异。然而紫杉醇加卡铂组有较好的生活质量,毒副作用均可耐受。     

CPE和CE方案治疗小细胞肺癌的疗效比较

目的　评价CPE(卡铂、顺铂、足叶乙甙)和CE(卡铂、足叶乙甙)方案治疗小细胞肺癌(SCLC)的疗效和毒性。方法　应用CPE和CE方案治疗32例SCLC患者,每组16例,CPE组和CE组中的复治病例分别为10例和7例。结果　CPE组和CE组的有效率分别为81.3%(13/16)和87.5%(14/16)(P>0.05)。CPE组与CE组中的复治病例有效率分别为60%(6/10)和42.9%(3/7)(P<0.05)。CPE组与CE组的骨髓抑制率分别为71.9%和93.8%(P<0.05)。两组间其它毒性反应差异无显著性(P>0.05)。结论　CPE方案治疗SCLC的疗效与CE方案相近,但CPE的骨髓抑制明显较CE轻;CPE对复治病例的疗效优于CE。     

卵巢上皮癌淋巴结转移化疗的临床疗效分析

背景与目的：卵巢上皮癌属化疗中度敏感肿瘤,随着肿瘤细胞减灭术及铂类联合化疗的应用,其疗效有明显改善,但其淋巴结转移病灶对化疗的敏感性尚存异议。本研究通过回顾性分析临床资料,以评价卵巢上皮癌患者淋巴结转移对化疗的敏感性及其预后,方法：对1986年6月－2001年2月收治的50例卵巢上皮癌淋巴结转移患者进行回顾性分析,其中Ⅲ-Ⅳ期32例,治疗后复发18例,50例均有可评价疗交的淋巴结转移灶,其中38例有可评价的盆腔,腹腔肿瘤。46例接受术前化疗1－3疗程,肿瘤细胞减灭术、术后化疗。化疗疗效评价按实体瘤疗效评价标准。化疗包括术前、术后或复发患者的化疗,其中45例接受含铂类联合化疗,包括CP（环磷酰胺＋顺铂）,CAP（环磷酰胺＋顺铂＋阿霉素或表阿霉素）,TC（紫杉醇＋卡铂）,TP（紫杉醇＋顺铂）,吉西他滨＋卡铂及IEP（顺铂＋异环磷酰胺＋足叶乙甙）方案,1例用美法仑,1例用CF（环磷酰胺和5－氟尿嘧啶）方案,3例用IFO＋VP－16（异环磷酰胺＋足叶乙甙）,结果：全组淋巴结转移灶和肿瘤的有效率分别为68．0％、71．1％,Ⅲ-Ⅳ期初治患者淋巴结转移和盆腹腔肿瘤有效率分别为78．1％,76．6％,而复发组两者有效率均为50．0％,结论：卵巢上皮癌的淋巴结转移,无论Ⅲ-Ⅳ期还是复发患者,其对化疗敏感性与盆腹腔肿瘤相近,Ⅲ-Ⅳ期患者预后与减瘤术是否彻底,以及化疗的疗程数多少有明显的相关性。     

Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer

BACKGROUND: Best supportive care has long been considered to be the standard therapy for metastatic non-small-cell lung cancer (NSCLC). There is now evidence from randomized trials that a number of chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival. We show how cost-effectiveness analyses can be used to make choices between different (ambulatory) chemotherapy regimens. METHODS: Clinical algorithms describing the diagnosis, staging, and treatment of metastatic NSCLC were incorporated into Statistics Canada's Population Health Model. Using consistent methodology, we assessed the cost-effectiveness of several chemotherapeutic interventions: a combination of vindesine (VDS) plus cisplatin, etoposide (VP-16) plus cisplatin, vinblastine (VLB) plus cisplatin, vinorelbine (Navelbine; NVB) plus cisplatin, paclitaxel (Taxol) plus cisplatin, and gemcitabine (GEM) and NVB alone. We calculated the total chemotherapy costs in 1995 Canadian dollars, the cost per case, the average life-years saved, and the cost per life-year saved. Using the Population Health Model, we then constructed an advanced decision framework that rank-ordered the various treatment regimens so as to optimize benefit below various cost-effectiveness thresholds. RESULTS: One regimen (VLB plus cisplatin) appears to result in better survival and lower health care expenditures than best supportive care. By use of cost-effectiveness thresholds of $25,000 and $50,000 per life-year gained, NVB plus cisplatin is the preferred regimen. When quality of life is considered, however, GEM is preferred to NVB plus cisplatin at a threshold value of $50,000. At thresholds of $75 000 and $100,000, paclitaxel plus cisplatin at a dose of 135 mg/m(2) is the preferred regimen. At thresholds of $50,000 and above, best supportive care is the least preferred regimen. CONCLUSIONS: This decision framework allows the comparison of different treatment regimens based on various cost-effectiveness thresholds. Our analysis also supports the use of chemotherapy regimens and the abandonment of best supportive care as the standard of care for patients with advanced NSCLC. [J Natl Cancer Inst 2000;92:1321-9].     

Irinotecan monotherapy offers advantage over combination therapy with irinotecan plus cisplatin in second-line setting for treatment of advanced gastric cancer following failure of fluoropyrimidine-based regimens

The optimal regimen of chemotherapy for gastric cancer in a second-line setting remains to be clarified. The aim of this retrospective study was to evaluate the efficacy and safety of second-line irinotecan treatment. A total of 134 patients with gastric cancer who had received prior chemotherapy with fluoropyrimidine-based regimens were treated with irinotecan (150 mg/m(2) on days 1 and 15) alone every 4 weeks (Arm I) or irinotecan (70 mg/m(2) on days 1 and 15) plus cisplatin (80 mg/m(2) on day 1) every 4 weeks (Arm IP) between April, 2004 and March, 2009. Patient characteristics, response rate, progression-free survival, overall survival and safety were investigated. Of 134 patients with recurrent or unresectable gastric cancer, 92 were treated in Arm I and 42 patients in Arm IP. Overall response rate in Arm I was 8.1%, compared with 20.0% in Arm IP (P=0.65). Median progression-free survival (Arm I vs. IP; 2.6 vs. 2.7 months, P=0.73) and median overall survival (Arm I vs. IP; 9.8 vs. 8.0 months, P=0.67) did not differ between the two treatment groups. Neutropenia, leukopenia and anorexia were the most common grade 3/4 adverse events, occurring significantly more frequently in Arm IP than in Arm I (P<0.05). Irinotecan may be a key agent, and serial irinotecan monotherapy is more beneficial as compared to irinotecan plus cisplatin in the treatment of advanced gastric cancer in second-line settings. Irinotecan monotherapy is beneficial compared to irinotecan plus cisplatin in second-line settings for the treatment of advanced gastric cancer refractory to fluoropyrimidine-based regimens.     

Cisplatin plus etoposide chemotherapy followed by thoracic irradiation and paclitaxel plus cisplatin consolidation therapy for patients with limited stage small cell lung carcinoma

PURPOSE: To evaluate the efficacy and tolerance of a cisplatin plus etoposide regimen followed by thoracic radiotherapy (TRT) and paclitaxel plus cisplatin consolidation chemotherapy in patients with limited stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-nine patients with limited SCLC were enrolled onto this study. Patients received three courses of cisplatin 75 mg/m2 i.v., day 1 and etoposide 100 mg/m2 i.v., days 1-3 (EP regimen), followed by TRT (45-56 Gy administered in 15 fractions), and three courses of paclitaxel 175 mg/m2 i.v., day 1 and cisplatin, as previously, on day 2 (PP regimen); cycles were repeated every 21 days. RESULTS: All patients were evaluable for toxicity and 34 for response. The overall response rate was 67% (CR: 26%; PR: 41%; intention-to-treat analysis) (95% CI: 53.0-84.2%). After a median follow-up period of 15 months, the median survival time was 15 months, the median time to tumor progression 8.3 months and the 1-year survival rate 53.8%. Grade 3/4 neutropenia occurred in 39% and 36% of patients receiving EP and PP regimens, respectively. The incidence of febrile neutropenia was 5% and 3% for EP and PP regimens, respectively. Other hematologic and non-hematologic toxicities were mild, with the exception of esophagitis occurring in 36% of patients during and/or immediately after radiotherapy. CONCLUSION: Consolidation therapy with PP after sequential EP and thoracic radiotherapy is feasible and well-tolerated; however, the efficacy results are comparable with those previously obtained in the same patients' population using a combination of EP and TRT.     

Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer

BACKGROUND:

Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost‐effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer.

METHODS:

A Markov decision‐analytic model was constructed to compare the cost‐effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity‐modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity.

RESULTS:

SBRT increased life expectancy by 0.20 quality‐adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost‐effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost‐effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost‐effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT.

CONCLUSIONS:

The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost‐effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by today's standards. Cancer 2012;. © 2011 American Cancer Society.     

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin–gemcitabine (GC) regimen (800 mg/m² gemcitabine on Days 1 and 8 and 20 mg/m² cisplatin on Days 1–5, every 4 weeks) (sGC‐RT); sequential chemoradiotherapy with a cisplatin–fluorouracil (PF) regimen (20 mg/m² DDP and 500 mg/m² 5‐FU on Days 1–5, every 4 weeks) (sPF‐RT) and cisplatin‐based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con‐RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3‐year overall survival (OS), disease‐free survival (DFS) and distant metastasis‐free survival (DMFS) rates in the sGC‐RT group were significantly higher than those observed in the Con‐RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3‐year OS, DFS and MFS rates between the Con‐RT and the sPF‐RT groups. The GC‐RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC‐RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.     

紫杉醇联合顺铂及长春瑞滨联合卡铂治疗老年晚期非小细胞肺癌的临床对照研究

为了探讨紫杉醇联合顺铂及长春瑞滨联合卡铂方案对老年晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的疗效和毒副反应,选取初治晚期NSCLC65例,分别应用TP(紫杉醇 顺铂)、NE(长春瑞滨 卡铂)方案治疗。每例均完成2个周期化疗后评价疗效及毒副反应。结果两组患者近期有效率TP组为41·9%(13/31),NE组为41·2%(14/34),差异无统计学意义,P>0·05。中位生存期TP组8·1个月,NE组7·2个月,差异无统计学意义,P>0·05。两组毒副反应均以骨髓抑制、脱发及恶心呕吐为主,TP组恶心呕吐发生率为87·1%,NE组为73·5%,白细胞减少TP组为74·9%,NE组为85·3%。两组病例均无化疗相关死亡发生。初步研究结果提示,TP、NE联合方案是治疗老年晚期NSCLC有效且耐受性较好的方案。     

Open-label feasibility study of pazopanib, carboplatin, and paclitaxel in women with newly diagnosed, untreated, gynaecologic tumours: a phase I/II trial of the AGO study group

Introduction:

Although most patients with advanced gynaecologic malignancies respond to first-line treatment with platinum-taxane doublets, a significant proportion of patients relapse. Combining targeted agents that have non-overlapping mechanisms of action with chemotherapy may potentially increase the disease-free interval. Accordingly, this study evaluated the feasibility of combining pazopanib, an oral angiogenesis inhibitor, with paclitaxel and carboplatin.

Methods:

This open-label, phase I/II study planned to evaluate the safety and efficacy of paclitaxel 175 mg m^–2 plus carboplatin (AUC5 (Arm A) or AUC6 (Arm B)) once in every 3 weeks for up to six cycles with either 800 or 400 mg per day pazopanib.

Results:

Dose-limiting toxicities (DLTs) were observed in two of the first six patients enrolled at pazopanib 800 mg plus paclitaxel 175 mg m^–2 plus carboplatin AUC5. Of the six patients enrolled in the next and lowest dosing level planned in the study, pazopanib 400 mg plus paclitaxel 175 mg m^–2 plus carboplatin AUC5, two patients also experienced DLTs and the study was terminated. Two of the 4 DLTs observed overall were gastrointestinal perforations. Severe myelotoxicity was reported in 6 of 12 patients.

Conclusion:

Combining either 800 or 400 mg per day pazopanib with standard carboplatin/paclitaxel chemotherapy is not a feasible treatment option.     

Refractory non-small-cell lung cancer responding to combination chemotherapy with docetaxel, gemcitabine and cisplatin

The combination of docetaxel (TXT), gemcitabine (GEM), and cisplatin (CDDP) produced a regression in a squamous cell carcinoma of the lung that had recurred after radiation therapy plus chemotherapy, and was resistant to the combination of carboplatin (CBDCA) with etoposide (ETP) or paclitaxel (TXL). The patient was a 62-year-old man with squamous cell lung cancer, which was first successfully treated by a combination of radiation therapy and chemotherapy, but showed local recurrence after 8 months. Although the recurrence was treated with CBDCA plus ETP and then TXL, the tumor continued to grow with symptomatic progression of airway stenosis. The tumor began to regress after the regimen of TXT, GEM and CDDP was started. This therapy achieved PR with symptomatic improvement. The combination of TXT, GEM and CDDP may be effective for recurrent non-small-cell lung carcinoma, even in patients that have failed to respond to more than one chemotherapy regimen.     

Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.