Retrospective analysis of carboplatin and paclitaxel as initial second-line therapy for recurrent epithelial ovarian carcinoma: application toward a dynamic disease state model of ovarian cancer.

PURPOSE: The majority of patients with epithelial ovarian cancer (EOC) who achieve a complete remission with front-line chemotherapy develop recurrent disease. Carboplatin and paclitaxel are used for patients with platinum-sensitive recurrent disease, although there is little information regarding the response and survival in unselected patients treated with this strategy. We sought to determine the outcomes for patients with EOC treated with carboplatin and paclitaxel at the time of first recurrence. In addition, we sought to define a new paradigm for disease transition in patients with EOC. PATIENTS AND METHODS: Eighty-nine patients were identified who had a complete response to front-line platinum-based chemotherapy for EOC, relapsed 6 months after completion of front-line chemotherapy, and were treated with carboplatin and paclitaxel as second-line therapy. RESULTS: Eighty-four cases were available for analysis of survival end points, and 66 were assessable for response. The median follow-up was 27 months. The overall response rate was 70%. The median progression-free interval for the cohort was 13 months (95% confidence interval [CI], 10.7 to 13.8 months). The 3-year survival rate was 72% (95% CI, 59.4 to 86.1%). Toxicity was limited, and no deaths from treatment were observed. Using this data, it is possible to construct a disease states model of EOC, which provides risk estimates for transitions between clinically distinct categories. CONCLUSION: Re-treatment with carboplatin and paclitaxel is effective as initial therapy in recurrent EOC. This should form the basis of a randomized trial to determine the best agents for initial treatment of relapse from EOC in potentially platinum-sensitive patients.     

Management of recurrent ovarian cancer with systemic therapy

The majority of patients with recurrent ovarian cancer receive palliative chemotherapy. Several factors have been identified as predictors of response, but the main factor related to second-line treatment response is platinum-free interval (PFI). Patients with a PFI of <6 months have a poor prognostic profile and can be described as platinum resistant, while those patients with a PFI of >6 months are described as platinum sensitive. In platinum-sensitive patients the goal is to prolong survival, whereas in platinum-resistant patients treatment can only produce palliative benefits. An alternative classification of ovarian cancer has been proposed relating to platinum-refractory disease. Patients with refractory disease are those who have progressive disease during treatment or those with a treatmentfree interval (TFI) of 4 months or less, intermediate group patients have a TFI of 4-12 months, while patients with sensitive-recurrent disease have a TFI of 12 months or more. Trial data have confirmed the superiority of platinum-based combination chemotherapy versus platinum monotherapy in platinum-sensitive patients. In patients pre-treated with paclitaxel plus carboplatin, a gemcitabine plus carboplatin combination is promising, avoiding alopecia, neurotoxicity and other toxicities, and may also benefit platinum-sensitive patients who have suffered early recurrence. Trials are currently under way for various compounds, including bevacizumab, erlotinib, pertuzumab, imatinib, enzastaurin, epothilones, topotecan and trabectedin. Clinical trials are also ongoing for combinations of molecular-targeting agents and conventional chemotherapeutics.     

Long-term results of weekly paclitaxel carboplatin induction therapy: An effective and well-tolerated treatment in patients with platinum-resistant ovarian cancer

BackgroundWeekly paclitaxel/cisplatin is effective in platinum-resistant epithelial ovarian cancer (EOC). To reduce toxicity, paclitaxel/cisplatin was replaced by paclitaxel/carboplatin.Patients and methodsPatients with progressive EOC after prior 3-weekly paclitaxel/carboplatin were treated with six cycles weekly paclitaxel 90 mg/m² and carboplatin area under the curve (AUC) 4 mg/ml/min, followed by six cycles 3-weekly paclitaxel/carboplatin. End-points were progression free survival (PFS), overall survival (OS), response rate (RR) and toxicity.ResultsMedian progression free interval after last platinum was 9 (0–81) months in 108 patients; 43 were platinum-resistant, of whom 13 started weekly paclitaxel/carboplatin <6 months after progression. During 633 weekly cycles grade 3/4 toxicity included; thrombocytopenia 8%, neutropenia 30%, febrile neutropenia 0.5%. Non-haematologic toxicity was low. Treatment was delayed in 16%, and dose reduced in 2% of cycles. RR was 58% for platinum-resistant and 76% for platinum-sensitive patients, median PFS were 8 (range 1–21) and 13 (1–46) months, median OS 15 (1–69) and 26 (4–93) months, respectively. The 13 platinum-resistant patients with a platinum-therapy free interval <6 months had a significant shorter PFS (4 versus 10 months, p = 0.035) and OS (9 versus 15 months, p = 0.002).ConclusionSix cycles weekly paclitaxel/carboplatin followed by six 3-weekly cycles is well-tolerated and highly active in platinum-resistant and platinum-sensitive patients.     

Weekly paclitaxel infusion as salvage therapy in ovarian cancer

The majority of women diagnosed with epithelial ovarian cancer will have persistent or recurrent disease after initial treatment. We evaluated response and toxicity in women with advanced stage disease given salvage paclitaxel as a low-dose, weekly infusion. We performed a retrospective review of 22 women with advanced stage epithelial ovarian (19 women) or primary peritoneal carcinoma (3 women) who had received low-dose, weekly paclitaxel salvage therapy. All women had refractory, persistent, or recurrent disease following first-line treatment with paclitaxel and platin chemotherapy. Response and toxicity were assessed. Measurable disease present on physical or radiologic exam and serum carbohydrate antigen-125 levels were used to assess disease response. Overall response rate to low-dose, weekly paclitaxel salvage therapy was 50% (27% complete, 23% partial). Median progression-free interval (PFI) in responders was 27 weeks (range, 14-68 weeks). Stabilization of disease occurred in an additional 27% of patients with a median PFI of 22 weeks (range, 15-89 weeks). No difference in response was detected between the 7 women with platin-sensitive disease and the 15 women with platin-resistant disease (P=0.19). The median dose of paclitaxel was 80 mg/m² (range, 60-80 mg/m²). During a total of 325 weeks of paclitaxel treatment (median per patient, 12 weeks; range, 6-49 weeks), 13 treatment delays occurred (hematologic indication, 9; nonhematologic indication, 4). No cases of grade 4 hematologic toxicity, sepsis, or worsening neuropathy were documented. Weekly paclitaxel infusion given as salvage therapy results in significant clinical response, even in women previously treated with paclitaxel. The regimen is well tolerated with no cases of grade 4 neutropenia or worsening neuropathy in our population.     

Chemotherapy with pegylated liposomal doxorubicin and cisplatin in recurrent platinum-sensitive epithelial ovarian cancer

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients. METHODS: Twenty-two women (median age, 57 years) with ovarian cancer that recurred 6 months or more after standard carboplatin and paclitaxel therapy were eligible for enrollment. Cisplatin was administered intravenously as a 60-min infusion on day 1, at a single dose of 60 mg/m(2), and PLD was given intravenously as a 1-h infusion on day 2, at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. RESULTS: Hematological toxicity was mainly leucopenia/neutropenia, and this was the principal dose-limiting toxicity. Severe (grade III-IV) leucopenia/neutropenia was observed in 7 (32%) and 9 (41%) patients, respectively. Only 2 (9%) patients were complicated by febrile neutropenia. Grade III-IV anemia occurred in only 4 (18%) patients. Severe thrombocytopenia was not noted; only 5 patients (23%) had grade I-II toxicity. NO toxicity in biochemical parameters was noted. Several severe nonhematological adverse effects were managed according to standard protocols and were transient, as well as being well-tolerated. Twenty-one patients were evaluated for response. The overall response rate was 62% (13 of 21; 95% confidence interval [CI], 38%-82%), with four (19%) complete and nine (43%) partial responses. At the time of last follow-up, all of the 22 patients were alive. The median follow-up period was 8.5 months (range, 2 to 22 months). CONCLUSION: PLD combined with cisplatin at the schedule and dosage used in this study is an active and safe second-line chemotherapy regimen with acceptable and easily manageable toxicities in women with platinum-sensitive recurrent ovarian cancer.     

Heavily pretreated ovarian cancer patients treated by single-agent gemcitabine. A retrospective outcome comparison between platinum-sensitive and platinum-resistant patients

To assess activity and toxicity of gemcitabine treatment in heavily pretreated epithelial ovarian cancer (EOC) patients and compare the outcome between platinum-sensitive and platinum-resistant patients. We conducted a retrospective analysis of 43 women with EOC treated with gemcitabine on Days 1, 8 and 15 every 28 days. Response was evaluated by physical examination and serial CA 125 measurements. The patients (median age 62 years, range 29-87) were previously exposed to a median of 3 (2-8) chemotherapy regimens. A median of 3.5 (1-14) gemcitabine cycles were administered. Eleven (25.6%) patients showed partial response, 19 (44.2%) had stable disease and 13 (30.2%) progressed. Among 22 platinum-sensitive and 21 platinum-resistant patients, the response rate was 45.5% and 4.7% respectively (p = 0.001), and the median time to progression was 5.0 and 2.8 months, respectively (p = 0.0006). The respective median survival was 16.5 and 6.3 months (p = 0.0001). Grade III-IV hematological toxicities included anemia in four (9.3%) patients, thrombocytopenia in four (9.3%) and leucopenia in two (4.7%). The main non-hematological toxicities were grade III fatigue in two patients (4.7%) and nausea and vomiting in two (4.7%). Single agent gemcitabine is an attractive option for heavily pretreated EOC patients. The significant difference between platinum-sensitive and resistant patients' warrants further investigation.     

Randomized phase II study of weekly paclitaxel versus paclitaxel and carboplatin as second-line therapy in disseminated melanoma: a multicentre trial of the Dermatologic Co-operative Oncology Group (DeCOG)

Stage melanoma IV has a poor prognosis, with a median survival time between 3 and 11 months from the diagnosis of distant metastases. Response rates in first-line regimens are around 20%. To date, no second-line treatment has been established. We performed a randomized, multicentre, second-line clinical phase II study of paclitaxel either as monotherapy or combined with carboplatin given on an outpatient basis. In arm A, paclitaxel was administered at a dose of 100 mg/m2 intravenously on day 1 each week for 6 weeks. In arm B, paclitaxel was administered at a dose of 80 mg/m2 intravenously followed by carboplatin 200 mg/m2 on day 1 each week for 6 weeks. The next cycle was administered after a 2 week intermission. The response rate, survival time, time-to-progression and toxicity were assessed in both arms. The study was stopped after 40 patients because the overall response rate was below 10% in both arms. The median survival time after initiation of second-line treatment was 209 days (+/- 196 days) for patients treated with paclitaxel only, and 218 days for those treated with paclitaxel/carboplatin. The median time-to-progression was around 56 days in both arms. Two partial responses were observed after 16 weeks, lasting for 8 and 12 weeks, respectively. Although both treatment modalities were well tolerated, haematological toxicity was higher in the combination arm. This is so far the largest second-line clinical phase II study reported in melanoma. However, paclitaxel with or without carboplatin had only limited efficacy, and the combination of these drugs adds significantly to haematological toxicity without improving response or survival rates.     

Monthly paclitaxel and carboplatin with oral estramustine phosphate in patients with hormone-refractory prostate cancer

Background We aimed to determine the safety and efficacy of monthly paclitaxel and carboplatin with oral estramustine phosphate in patients with hormone-refractory prostate cancer (HRPC). Methods Patients with prostate cancer that was progressing despite androgen ablation therapy were treated with i.v. paclitaxel, 175 mg/m², over 3 h, followed by carboplatin (area under the curve, 5) on day 1, with oral estramustine phosphate, 280 mg twice daily, for a 28-day treatment cycle. Estramustine phosphate was precluded in those patients who had experienced adverse effects during prior chemotherapies. Patients were evaluated for response every cycle, and the treatment was continued until the cancer progressed. Results Twenty-one patients with progressive hormone-refractory disease were treated for a median of 4 cycles (range, 1 to 11 cycles). Estramustine phosphate was precluded in seven patients. Post-therapy decreases in serum prostate-specific antigen levels of 50% and 75%, respectively, were seen in 43% and 19% of the patients (95% confidence intervals, 22% to 64% and 2% to 36%). Of the nine patients with measurable disease, 1 (11%) had a complete response and 2 (22%) had a partial response. The overall median time to progression was 4 months, and the median survival time for all patients was 11 months. Major grade 3 or 4 adverse effects were anemia (29%), neutropenia (48%), and thrombocytopenia (24%). Mild peripheral neuropathy and myalgia/arthralgia were observed in 11 (52%) and 9 (43%) patients, respectively. Conclusion Monthly paclitaxel and carboplatin with oral estramustine phosphate has significant antitumor activity and is well tolerated in patients with progressive HRPC.     

Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma

BACKGROUND: Patients with metastatic melanoma (MM) have very few therapy options. Based on reports of responses to paclitaxel and carboplatin (PC), 31 patients with MM were treated with PC. METHODS: Data regarding patients treated with PC were abstracted from medical records. Clinical outcomes as determined by the treating oncologist were used for this analysis. Response determination was retrospectively confirmed using Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Thirty-one patients with MM were treated with PC. Patients had a median of 2 previous therapies, with the majority (29; 94%) having failed prior temozolomide (TMZ) or dacarbazine (DTIC) therapy. The most commonly used regimen was weekly paclitaxel (at a dose of 100 mg/m(2)) and carboplatin (area under the curve 2) administered on Days 1, 8, and 15 of a 28-day cycle. An objective partial response was noted in 8 patients (26%) with an additional 6 patients (19%) having stable disease; therefore, a clinical benefit was noted in 45% of those patients treated. The median time to disease progression for the entire group was 3 months (range, 0-7 mos), with a median overall survival of 7.8 months (range, 1-14 mos). The clinical benefit derived by the 14 patients, which lasted for a median of 5.7 months (range, 2.5-7.3 mos), was considered to be clinically significant. At the time of last follow-up, eight patients continued to receive PC therapy. CONCLUSIONS: The PC combination appears to have definite and clinically meaningful activity when used as second-line therapy after TMZ or DTIC. Further evaluation of this regimen, alone or as a 'backbone' for other agents, needs to be considered.     

Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer.

PURPOSE: To determine the response rate of trastuzumab as first-line therapy in patients with HER-2 overexpressing metastatic breast cancer. To assess the feasibility and toxicity of weekly paclitaxel/carboplatin with or without trastuzumab following initial treatment with trastuzumab. PATIENTS AND METHODS: Sixty-one patients received trastuzumab (8 mg/kg followed by 4 mg/kg/wk) for 8 weeks. Responding patients received 8 additional weeks of trastuzumab (4 mg/kg/wk), and then proceeded to receive trastuzumab (2 mg/kg) in combination with paclitaxel 70 mg/m(2) and carboplatin (area under the curve, 2) weekly for 6 weeks followed by 2 weeks rest. Stable patients after the initial 8 weeks of trastuzumab proceeded to treatment with trastuzumab, paclitaxel, and carboplatin. Patients with disease progression during the initial 8 weeks had the trastuzumab discontinued and were treated with weekly paclitaxel/carboplatin. RESULTS: Weekly paclitaxel/carboplatin with or without trastuzumab was well tolerated. Fifty-two patients were assessable for response and all 61 patients were assessable for survival. Seventeen (33%) of 52 patients experienced a minor/partial response to single-agent trastuzumab and received 8 additional weeks of single-agent trastuzumab. Fifteen (29%) of 52 patients had stable disease and proceeded to receive paclitaxel/carboplatin/trastuzumab. Thirty-one patients with measurable disease were assessable for response after initial single-agent trastuzumab followed by paclitaxel/carboplatin/trastuzumab. An overall response rate of 84% (eight complete responses/18 partial responses), median time to progression of 14.2 months, and median overall survival of 32.2 months was reported with the triplet combination. In the patients treated with paclitaxel/carboplatin alone after disease progression on initial single-agent trastuzumab, an overall response rate of 69% (one complete response/10 partial responses), median time to progression of 8.3 months, and median overall survival of 22.2 months was reported. Median time to progression for all 61 patients is 10 months and the median overall survival is 26.7 months. CONCLUSION: This trial confirms the activity and tolerability of weekly paclitaxel/carboplatin alone or in combination with trastuzumab in women with HER-2 overexpressing metastatic breast cancer.     

Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer.

PURPOSE: To compare four cycles of therapy versus continuous therapy to determine the optimal duration of chemotherapy in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB/IV NSCLC patients were randomized to arm A (four cycles of carboplatin at an area under the curve of 6 and paclitaxel 200 mg/m(2) every 21 days) or arm B (continuous treatment with carboplatin/paclitaxel until progression). At progression, all patients on both arms were to receive second-line weekly paclitaxel at 80 mg/m(2)/wk. The primary end points were survival and quality of life (QOL). RESULTS: Two hundred thirty patients were randomized. Fifty-seven percent of arm A patients completed four courses of therapy. In the 116 arm B patients, the median number of cycles delivered was four (range, zero to 19 cycles). Forty-two percent received five or more cycles; 18% received eight or more cycles. Overall response rates were 22% and 24% for arms A and B, respectively (P =.80). Median survival time and 1-year survival rates were 6.6 months and 28% for arm A and 8.5 months and 34% for arm B, respectively (log-rank P =.63). Rates of hematologic and nonhematologic toxicity were similar between the two arms, except for neuropathy. The rate of grade 2 to 4 neuropathy increased from 19.9% (95% confidence interval [CI], 13.6% to 26.2%) at cycle 4 to 43% (95% CI, 28.6% to 57.4%) at cycle 8. There were no differences in QOL. Only 45% of patients received second-line therapy (42% in arm A v 47% in arm B, P =.42). CONCLUSION: This study shows no overall benefit in survival, response rates, or QOL to continuing treatment with carboplatin/paclitaxel beyond four cycles in advanced NSCLC.     

Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy

Background  The objective of this study was to evaluate the efficacy and toxicity of combination chemotherapy with gemcitabine and paclitaxel as a second-line regimen in patients with advanced urothelial carcinoma. Methods  Twenty patients with advanced urothelial carcinoma who were resistant to an M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy regimen were administered chemotherapy consisting of intravenous gemcitabine 2500 mg/m² and paclitaxel 150 mg/m² (GP) every 2 or 3 weeks. Results  The patients received a median of 7.7 cycles of treatment (range, 2–20 cycles). Six of the 20 patients (30%; 95% confidence interval [CI], 10%–50%) had a major response to treatment (a complete response [CR] in 5% and a partial response [PR] in 25%). Seven patients (35%) had stable disease (SD). The median duration of response was 4.5 months (range, 1–9 months) and the disease control rate (CR + PR + SD) was 65%. The median survival was 11.5 months (range, 2–22 months) and the 1-year survival rate was 35%. The patients tolerated this regimen well, with only grade 3–4 neutropenia being observed in 6 patients (30%), anemia in 3 (15%), and thrombocytopenia in 1 (5%). The response rate to M-VAC in the first-line chemotherapy was significantly associated with the response to GP as the second-line chemotherapy. Conclusion  The combination of gemcitabine and paclitaxel is active and well tolerated as a second-line treatment in patients with advanced urothelial carcinoma.     

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-na?ve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.     

A phase II trial of weekly paclitaxel and gemcitabine in non-small cell lung cancer patients previously treated with platinum and vinorelbine

This study evaluated the activity and toxicity of a weekly paclitaxel plus gemcitabine combination as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel 80 mg/m2 on days 1, 8 and 15 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks were administered to 34 consecutive, advanced NSCLC patients uniformly pretreated with cisplatin or carboplatin and vinorelbine. The median time interval from first- to second-line treatment was 8 weeks (range 1-72). A total of 124 cycles with a median of 3 cycles per patient were administered (range 1-6). Four patients (12%) achieved a partial response (95% confidence interval: 1-23%), 17 had stable disease (50%) and 12 progressed (37%). Three responses were observed in 14 patients showing disease response or stabilization to previous platinum therapy. The median survival was 28 weeks (range 3-91), the median progression-free survival was 12 weeks (range 3-50) and the 1-year survival rate was 23%. The toxicity profile was favorable. In conclusion, a weekly schedule of paclitaxel plus gemcitabine as a second-line regimen has moderate activity and good tolerability in NSCLC patients not refractory to previous platinum-vinorelbine treatment.     

曲妥珠单抗治疗141例人表皮生长因子受体2阳性乳腺癌的回顾性分析

目的 总结曲妥珠单抗在人表皮生长因子受体2(Her-2)阳性乳腺癌患者新辅助、辅助和复发转移治疗中的临床应用经验,评价其与化疗联用的疗效.方法 对2004年1月至2008年12月门诊应用曲妥珠单抗治疗的141乳腺癌患者进行回顾性分析.随访时间为3～319个月.分析患者的无病生存时间(DFS),比较患者辅助、复发转移一线及二线使用曲妥珠单抗治疗的总生存时间(OS)、治疗失败时间(TTF)和临床有效率的差异.结果 与曲妥珠单抗治疗联用的新辅助化疗中,紫杉醇联合卡铂方案占66.7%;辅助治疗中,蒽环类和蒽环类序贯紫杉类方案占53.9%.复发转移的患者治疗后中位DFS为17个月.复发转移的患者经一线曲妥珠单抗联合化疗治疗后,临床总有效 率为84.5%,中位TTF为24个月;二线治疗有效率为44.4%,中位TTF为5个月.两者比较,差异有统计学意义(P=0.002).结论 紫杉醇和卡铂化疗联合曲妥珠单抗,值得在新辅助治疗中推广,紫杉类和蒽环类联合或序贯靶向治疗仍是辅助治疗的标准方案.转移性乳腺癌一线应用曲妥珠单抗联合化疗比二线治疗的临床有效率更高,在继续应用曲妥珠单抗的基础上改用化疗方案,可提高治疗有效率,减少治疗失败的概率.     

Treatment Outcomes of Paclitaxel for Refractory or Recurrent Epithelial Ovarian Cancer Patients in Thailand

Background: To study the response rate, toxicity profiles, and survival of refractory or recurrent epithelialovarian cancer (EOC) patients treated with paclitaxel. Materials and Methods: Patients with refractory orrecurrent EOC who were treated with paclitaxel between January 2002 and December 2011 at the Departmentof Obstetrics and Gynecology, Faculty of Medicine, Vajira Hospital were identified. Clinicopathological featuresof the patients including detailed data of paclitaxel treatment were collected. Results: During the study period, atotal of 44 patients were identified, with a mean age of 52.9±8.2 years. Some 13.6% (six patients) had refractorycancer to first-line chemotherapy while 86.4% (38 patients) had recurrent cancer. Among these, 35 (79.6%)and 9 (20.4%) patients were considered as platinum-sensitive and platinum-resistant, respectively. Threepatients (6.8%) received fewer than 2 cycles of paclitaxel due to loss to follow-up, leaving 41 patients evaluablefor response. The overall response rate observed in all 41 patients was 41.5% (17 patients; 12 complete andfive partial responses): 12.5% or 1/8 patients with refractory or platinum-resistant cancer and 48.5% or 16/33patients with platinum-sensitive disease. Stable disease was demonstrated in 17.0% (seven patients) whileprogressive disease was apparent in 41.5% (17 patients). Median time to progress was 4.5 months (range, 0.67-58.6 months). Median progression-free survival was not reached while median overall survival was 16.3 months(95% confidence interval, 11.0 months -21.6 months). Common toxicities were neutropenia, neuropathy, andalopecia. Conclusions: Paclitaxel is an active agent for refractory or recurrent EOC. Neutropenia, neuropathyand alopecia are common side effects.     

Gemcitabine plus carboplatin combination therapy as second-line treatment in patients with relapsed breast cancer

This study was designed to determine the safety and efficacy of the combination therapy of gemcitabine plus carboplatin when used as a second-line treatment in patients with metastatic breast cancer (MBC). From February 2002 to May 2003, 30 previously treated patients with adenocarcinoma of the breast received gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin to an area under the curve (AUC) of 5 on day 1. The carboplatin dose was changed to an AUC of 4.5 because of toxicity, with cycles repeated every 3 weeks. Among 30 patients enrolled, 25 were assessable for response rate (RR). There was no complete response; 9 patients (30%) had partial response, for an overall RR of 30%. The median time to progression for the study group was 20.47 weeks (range, 8-46 weeks). Treatment-related toxicities included grade 3/4 neutropenia in 50% of patients (20% of whom had febrile neutropenia), grade 3/4 anemia in 26.6% of patients, and grade 3/4 thrombocytopenia in 30%. Eleven patients (36.67%) had grade 1 alopecia, and 1 patient (3.33%) had grade 2 alopecia. Moderate nausea was observed in 8 patients (26.67%), and vomiting occurred in 7 patients. Four patients had asthenia and 3 (10%) experienced stomatitis. Three patients discontinued treatment because of hematologic toxicity (thrombocytopenia) and 2 patients are still receiving treatment. Carboplatin plus gemcitabine is an active combination for patients with MBC despite significant but manageable hematologic toxicity.     

Phase II study of cisplatin-combined schedules as second-line chemotherapy in patients with non-small cell lung cancer

BACKGROUND: The aim of this study was to evaluate the effectiveness of cisplatin- (CDDP) combined chemotherapy in non-cisplatin pretreated patients with non-small-cell lung cancer (NSCLC). The second cytotoxic drug administered was either etoposide or gemcitabine. First-line treatment was based on paclitaxel combined with either carboplatin or vinorelbine. PATIENTS AND METHODS: Seventy-eight patients with histologically- or cytologically- confirmed NSCLC, having failed front-line treatment, were enrolled. All patients received 80 mg/m2 of cisplatin as second-line treatment, on day 1, repeated every 3 weeks; in 48 patients the second agent was etoposide (120 mg/m2) on days 1, 2 and 3, repeated every 3 weeks and in 30 patients 1 g/m2 of gemcitabine on day 1, repeated every 3 weeks. RESULTS: All patients were evaluable for response and toxicity. No complete responses were observed. Thirteen (16.67%) patients achieved partial response, 42 (53.85%) stable disease and 23 (29.49%) had disease progression. The median duration of response was 4 months (range 2-8+ months), median time to tumor progression (TTP) 5 months (range 2-9 months) and median survival time after starting second-line chemotherapy, 6 months (range 2-9+ months). Toxicity was acceptable: 9 patients presented with nephrotoxicity (11.54%) and 13 (16.67%) with grade 3-4 neutropenia. CONCLUSION: The cisplatin combination as second-line treatment in patients with NSCLC exhibited a notable degree of activity and tumor growth control was evidenced by the 16.67% partial response and 53.85% disease stability.     

Carboplatin/etoposide/paclitaxel in the treatment of patients with extensive small-cell lung cancer

The purpose of this study was to examine the safety and efficacy of carboplatin/etoposide/paclitaxel in patients with untreated stage IV non-small-cell lung cancer (NSCLC) and extensive small-cell lung cancer (SCLC). Carboplatin was administered intravenously (i.v.) at an area under the curve (AUC) of 6 with etoposide at either 80 or 100 mg/m2 i.v. days 1-3 and paclitaxel at 175 or 200 mg/m2 i.v. over 3 hours along with 5 g/kg of granulocyte colony-stimulating factor subcutaneously on days 4-18, repeated every 3 weeks for 6 courses. Thirty-one patients (five NSCLC and 26 SCLC) entered into this phase I study. The median age was 63 (range, 42 to 74 years), with 24 males and seven females. The recommended dose level for phase II testing was carboplatin AUC = 6, etoposide 80 mg/m2 days 1-3, and paclitaxel 175 mg/m2 over 3 hours. With seven patients at this level, 14% had grade 4 neutropenia, 14% had grade 4 thrombocytopenia, none had grade 2/3 neurotoxicity, and no toxic deaths occurred. One of five (20%) patients with NSCLC responded, and 19 of 22 (86%) evaluable SCLC patients experienced a response to therapy. SCLC patients had a median survival of 10 months. The combination of carboplatin/etoposide/paclitaxel has significant activity with acceptable toxicity in patients with extensive SCLC.     

Sequential combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: carboplatin and gemcitabine followed by paclitaxel.

BACKGROUND: The objective of this Phase II study was to evaluate the concept of sequential chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC) by the administration of carboplatin plus gemcitabine followed by of paclitaxel. METHODS: Patients with Stage IIIB (pleural effusion) or Stage IV NSCLC and a Southwest Oncology Group (SWOG) performance status (PS) of 0--2 were eligible. Therapy consisted of three cycles of carboplatin (area under the concentration-time curve = 5.5 mg/mL per minute) on Day 1 and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days followed by three cycles of paclitaxel 225 mg/m(2) every 21 days. RESULTS: Of the 37 eligible patients, 81% had Stage IV disease, and 27% had a PS of 2; all were assessable for survival and toxicity; 32 patients were assessable for response. After treatment with carboplatin plus gemcitabine, there were no complete responses (CRs) and eight partial responses (PRs) (response rate [RR], 25%; 95% confidence interval [95% CI], 11--43%). The best overall response was two CRs and eight PRs (RR, 31%; 95% CI, 16--50%). The median survival time was 9.5 months, the 1-year survival rate was 36% (95% CI, 26--44%), the 2-year survival rate was 11% (95% CI, 3--25%), and the median time to disease progression was 4.9 months. The median survivals were 11.2 months for patients with a PS of 0--1 and 6.4 months for patients with a PS of 2. Noncumulative, reversible thrombocytopenia was the principal toxicity with carboplatin/gemcitabine therapy. Paclitaxel therapy was well tolerated, and moderate (Grade 3) neutropenia was the primary toxic effect. One cardiac death occurred, possibly related to paclitaxel. CONCLUSIONS: This study is the first to evaluate planned sequential chemotherapy in patients with NSCLC. Carboplatin plus gemcitabine followed by paclitaxel was well tolerated and resulted in promising survival in this patient population. This pilot experience forms the basis for an ongoing SWOG trial. Cancer 2001;92:146-52. Published 2001 American Cancer Society.