Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma

Purpose: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients.Patients and methods: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naïve patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible.Results: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3–4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive.Conclusions: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.     

两种方案治疗转移性乳腺癌的临床评价与药物经济学分析

  目的  从药物经济学角度对紫杉醇联合卡铂或表柔比星两种转移性乳腺癌化疗方案进行分析,为临床用药提供参考。  方法  采用成本-效果分析法对TP、TE(T:紫杉醇,P:卡铂,E:表柔比星)两种方案进行临床病例的回顾性分析比较。  结果  中位随访期为23.5(9~42)个月,TP、TE两组方案的有效率分别为78.33%和80.00%;1年、2年无进展生存率分别为43.6%和38.9%、10.8%和17.4%;1年、2年总生存率分别为80.3%和78.3%、53.2%和47.9%,两组之间无统计学差异(P>0.05)。成本-效果分析结果表明,两方案治疗成本分别为10 303.8元和13 853.3元,成本/效果比分别为131.54和173.17(P < 0.01)。化疗不良反应方面,TP组脱发发生率明显低于TE组(P < 0.01)。  结论  两方案近期与远期疗效相当,TP方案成本-效果高于TE方案,可作为晚期乳腺癌的优选方案之一。      

A phase II study of carboplatin and paclitaxel in esophageal cancer.

BACKGROUND: This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with esophageal cancer. MATERIALS AND METHODS: Thirty-five patients were enrolled. Patients were treated with paclitaxel 200 mg/m(2) intravenously (i.v.) over 3 h and carboplatin i.v. at an AUC of 5 mg/h/ml. Thirty-three patients were assessable for toxicity and objective response. RESULTS: A total of 166 treatment courses were administered with a median of five courses per patient. The objective response rate was 43% [90% confidence interval (CI) 0.3-0.58] by the intention-to-treat analysis. The median response duration was 2.8 months (90% CI 2.1-5.4). The median survival time was 9 months (90% CI 7-13.8) and the 1-year survival rate was 43% (90% CI 0.29-0.57). The major grade 3-4 toxicity observed was neutropenia, occurring in 17 patients (52%). There were no treatment-related deaths. CONCLUSIONS: The combination of carboplatin and paclitaxel is an moderately active and tolerable regimen in advanced esophageal cancer.     

A phase I-II study of bi-weekly paclitaxel as first-line treatment in metastatic breast cancer

Background: Single-agent bi-weekly paclitaxel was studied as first-line metastatic treatment for breast cancer in a phase I–II trial.Patients and methods: Thirty-eight women with metastatic breast cancer were enrolled. Thirty-seven are evaluable for toxicity, 35 for response.Results: The MTD was defined at 160 mg/m2 q two weeks with dose limiting toxicity in two patients consisting of hematological toxicity (1) and neurotoxicity (2). Twenty patients were treated at 150 mg/m2, the recommended dose. Response rates were two CRs and nine PRs (overall 61%) at the RD of 150 mg/m2 and three CRs and 11 PRs for an overall RR of 67% for the two top doses.Conclusions: The good drug tolerance, response rates, and convenience over weekly treatment suggest this may be a worthwhile regimen.     

A randomized phase 2 study of temozolomide and bevacizumab or nab‐paclitaxel,carboplatin, and bevacizumab in patients with unresectable stage IV melanoma

BACKGROUND:

Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM).

METHODS:

A phase 2 trial was conducted in chemotherapy‐naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m² on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab‐paclitaxel (100 mg/m², or 80 mg/m² post‐addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post‐addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression‐free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%.

RESULTS:

Ninety‐three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%‐51.2%) for TB and 56.1% (90% confidence interval: 44.7%‐70.4%) for ABC.

CONCLUSIONS:

The addition of bevacizumab to nab‐paclitaxel and carboplatin shows promising activity despite tolerability issues. Cancer 2013. © 2012 American Cancer Society.     

A pilot study of paclitaxel combined with gemcitabine followed by interleukin-2 and granulocyte macrophage colony-stimulating factor for patients with metastatic melanoma

It has been suggested that paclitaxel and gemcitabine modulate the immune system. This paper reports the safety and efficacy of paclitaxel plus gemcitabine followed by interleukin-2 (IL-2)and granulocyte macrophage colony-stimulating factor (GM-CSF), the PGIG chemobiotherapy, for patients with metastatic melanoma. All patients received 175 mg/m² paclitaxel on day 1 and 800 mg/m² gemcitabine on day two. IL-2 and GM-CSF were administered from day 4 to day 8 at a dosage of 2 MIU/m² and 100 μg, respectively. The PGIG chemobiotherapy was repeated every 21 d. Serum cytokine levels at baseline and at the end of the second cycle were measured via flow cytometry. Twenty-seven patients with metastatic melanoma accepted PGIG chemobiotherapy from August 2009 to March 2011. There were five patients that exhibited a partial response, 14 patients that exhibited a stable response and eight that displayed progressive disease. Therefore, the response rate was 18.5%, and the disease control rate was 70.4%. The median time to progression and median survival were 4 mo and 8 mo, respectively. The one-year and two-year survival rates were 25.9% and 18.5%, respectively. Frequent side effects included chills, fever, arthralgia, rash and pruritus. Among the 13 patients who experienced a rash and pruritus and the 14 patients who did not suffer from this side effect, the response rates and disease control rates were 30.8% vs 7.1% and 77% vs 64.2%, respectively. No relationship between serum IL-6 levels, clinical response, and either skin side effect was observed. The PGIG chemobiotherapy is safe and effective for the treatment of patients with advanced melanoma, but randomized trials are necessary to validate this effect.     

A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group Study, N057E(1)

BACKGROUND:

There is increasing evidence that paclitaxel and carboplatin are clinically active in the treatment of metastatic melanoma (MM). ABI‐007 is an albumin‐bound formulation of paclitaxel that has demonstrated single‐agent activity against metastatic melanoma.

METHODS:

A parallel phase II trial was conducted in patients with unresectable stage IV melanoma who were either chemotherapy naive (CN) or previously treated (PT). The treatment regimen consisted of ABI‐007 (100 mg/m²) and carboplatin area under the curve (AUC2) administered on days 1, 8, and 15 every 28 days. The primary aim of this study was objective response rate (RECIST).

RESULTS:

Seventy‐six patients (41 CN and 35 PT) were enrolled between November 2006 and July 2007. Three patients withdrew consent prior to starting treatment. The median number of treatment cycles was 4. There were 10 (25.6%) responses (1 complete response [CR] and 9 partial responses [PRs]) in the CN cohort (90% CI, 16.7%‐42.3%) and 3 (8.8%) responses (3 PRs) in the PT cohort (90% CI, 2.5%‐21.3%). Median progression‐free survival was 4.5 months in the CN cohort and 4.1 months in the PT cohort. Median overall survival (OS) was 11.1 months in the CN group and 10.9 months in the PT group. Severe toxicities in both groups (Common Terminology Criteria for Adverse Effects v.3.0 ≥grade 3) included neutropenia, thrombocytopenia, neurosensory problems, fatigue, nausea, and vomiting.

CONCLUSIONS:

The weekly combination of ABI‐007 and carboplatin appears to be moderately well tolerated, with promising clinical activity as therapy in patients who are chemotherapy naive and with modest antitumor activity in those previously treated. Cancer 2011. © 2010 American Cancer Society.     

A phase II study of weekly paclitaxel and carboplatin in previously untreated patients with advanced non-small-cell lung cancer

Purpose: Both paclitaxel (P) and carboplatin (C) have a significant activity in non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose intense, and has a favorable toxicity profile. To evaluate the efficacy and toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II study in patients with advanced NSCLC (III B with pleural effusion and stage IV). Patients and Methods: Eligible patients were treated with paclitaxel 100 mg/m² intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This treatment was administered weekly for 3 of every 4 wk until disease progression or intolerable toxicities. Results: Of the 30 patients enrolled in the study, one patient did not meet the eligibility criteria. Of the remaining 29 patients, 6 did not complete at least two cycles of treatment and hence were not assessable for response. The overall response rate was 43.5% (10/23) (all partial responses). An additional 43.5% had stable disease. The median time to progression was 162 d and the median duration of response was 169 d. Overall survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8 mo. We observed the following grade 3/4 toxicities: hypersensitivity to paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%), thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced grade 2 neuropathy. Conclusions: We conclude that weekly paclitaxel and carboplatin is active and very well tolerated in patients with advanced NSCLC.     

Phase II study of the combination carboplatin and paclitaxel in patients with ovarian cancer

Background: Recently the feasibility of combining carboplatin withpaclitaxel has been demonstrated in dose-finding studies. Maximum tolerateddoses were 550 mg/m² and 200 mg/m² (threehours), respectively. We report now a phase II study in ovarian cancerpatients.Patients and methods: Twenty-one chemo-naïve patients with optimally(n = 6) or suboptimally (n = 15) debulked stage III or IV ovarian cancer weretreated every three weeks for six courses with paclitaxel (200mg/m²) as a three-hour infusion, immediately followed bycarboplatin (550 mg/m²) as a 30-minute infusion.Results: Uncomplicated neutropenia was the principal toxicity, with mildanemia occurring regularly. As observed in the preceding phase I study, arelative lack of thrombocytopenia, generally grade III was found. Othertoxicities consisted of mild neurotoxicity, nausea and vomiting, alopecia,myalgia, and bone pain. All suboptimally debulked patients responded totherapy. Overall, 12 patients underwent second-look laparoscopy, whichrevealed a pathologically confirmed complete remission in six. The medianfollow-up interval at the time of analysis was 14 months. Twelve patients arecurrently free of progression, at 8+ to 19± months after the start oftherapy.Conclusion: The carboplatin/paclitaxel combination appears to be awell-tolerated regimen, yielding high response rates. This combination has nowgone forward to be evaluated in prospective randomized trials versus thecisplatin/paclitaxel combination.     

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma.

BACKGROUND: Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. PATIENTS AND METHODS: Chemotherapy na?ve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. RESULTS: Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. CONCLUSIONS: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).     

Interleukin-2 improves tumour response to DNP-modified autologous vaccine for the treatment of metastatic malignant melanoma

This paper is a report of response rate (RR) and survival of 34 metastatic melanoma patients who received a dinitrophenyl (DNP)-modified autologous melanoma cell vaccine. In all, 27 patients started the vaccine as a primary treatment for metastatic melanoma and seven started it as an adjuvant, with no evidence of disease at the time, but had developed new metastases. Interleukin-2 (IL-2) was administered in 24 out of the 34 patients: 19 who progressed on vaccine alone and five who had the combination from start. Interleukin-2 was administered in the intravenous, bolus high-dose regimen (seven patients) or as subcutaneous (s.c.) low-dose treatment (17). Overall response for the entire group was 35% (12 patients out of 34), 12% having a complete response (CR) and 23% a partial response (PR). However, only two patients had tumour responses while on the vaccine alone, whereas the other 10 demonstrated objective tumour regression following the combination with IL-2 (two CR, eight PR), lasting for a median duration of 6 months (range 3-50 months). Of the 12 responding patients, 11 attained strong skin reactivity to the s.c. injection of irradiated, unmodified autologous melanoma cells. None of the patients with a negative reactivity experienced any tumour response. Patients with positive skin reactions survived longer (median survival - 54 months). The results suggest enhanced RRs to the combination of IL-2 and autologous melanoma vaccine. Skin reactivity to unmodified autologous melanoma cells may be a predictor of response and improved survival, and therefore a criterion for further pursuing of immunotherapeutic strategies.     

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer

A total of 53 women with chemotherapy-na?ve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.     

Phase II study of paclitaxel and carboplatin in advanced gastric cancer previously treated with 5-fluorouracil and platinum

BACKGROUND: The combination of paclitaxel and carboplatin has been used to treat patients with many types of tumor, including gastric cancer. We evaluated the efficacy and safety of this combination in advanced gastric cancer patients previously treated with 5-fluorouracil and platinum. METHODS: Patients who had pathologically been proven to have measurable lesions were treated with paclitaxel (200 mg/m(2) for 3 h) and carboplatin [area under the concentration-time curve (AUC = 6)] on day 1 and in 21 day cycles. RESULTS: A partial response was achieved in 10 of 45 patients [22%, 95% confidence interval (CI), 10-34]. Of the 32 patients previously treated with cisplatin, four (13%) achieved partial response, whereas, of the 13 patients previously treated with heptaplatin, six (46%) achieved partial response. In all patients, the median time to progression was 14 weeks (95% CI, 10-18), and the median overall survival was 32 weeks (95% CI, 26-38). The most common grade 3/4 adverse events were neutropenia (40% of patients) and neuropathy (2.2%). Two patients developed neutropenic fever. However, there were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with paclitaxel and carboplatin is feasible in patients with advanced gastric cancer who were previously treated with 5-fluorouracil and platinum.     

Experience with interferon alpha 2b combined with dacarbazine in the treatment of metastatic malignant melanoma

A prospectively randomized trial was undertaken to compare dacarbazine (DTIC) alone with DTIC plus interferon in patients with metastatic malignant melanoma. Of the 73 patients who entered on the study, 36 were randomized to receive DTIC alone and 37 were randomized to receive the combination DTIC plus interferon. The two sections were well balanced. There was more toxicity on the combination section, but no life threatening toxicity. The overall response rate for patients on DTIC was 20% (two complete and five partial responses)(95% CI 7–39%) and for patients on DTIC plus interferon was 50% (13 complete and four partial responses)(95% CI 26–72%) (p=0.007). The median time to treatment failure, was significantly more in favour of the combination treatment (9versus 2.5 months;p < 0.01, Mantel-Cox). The median survival of 16.7versus 8 months was in favor of the combination treatment (p < 0.01). The reasons for the improved results with the combination treatment are discussed. The Eastern Cooperative Oncology Group is currently, based on the results of this study, investigating the role of interferon combinations in metastatic malignant melanoma     

A randomized phase II trial comparing every 3-weeks carboplatin/paclitaxel with every 3-weeks carboplatin and weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: The optimal schedule of taxane administration has been an area of active interest in several recent clinical trials. METHODS: To address a pure schedule question, we randomized 161 patients with advanced stage IIIB or IV non-small-cell lung cancer (NSCLC) to either paclitaxel 225 mg/m2 every 3 weeks x 4 cycles or 75 mg/m2/week x 12 (cumulative dose on each arm = 900 mg/m2). Both arms received concurrent carboplatin AUC 6 every 3 weeks x 4 cycles. RESULTS: The two arms were well-balanced in terms of known prognostic factors. The overall response rate and survival outcomes were similar on the two arms. There was significantly more grade 3/4 thrombocytopenia and grade 2-4 anemia on the weekly arm but less severe myalgias/arthralgias and alopecia. No difference in the rates of peripheral neuropathy was observed; however, patients on the every 3 weeks arm reported significantly more taxane therapy-related side-effects on the functional assessment of cancer therapy taxane subscale. CONCLUSIONS: This randomized trial exploring schedule-related issues with carboplatin/paclitaxel confirms the versatility of this regimen.     

Protective effect of amifostine against toxicity of paclitaxel and carboplatin in non-small cell lung cancer

Aim: In this study we determined the protective role of amifostine against the side effects of the combination of paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). Patients and Methods: Chemo-naive patients with NSCLC were eligible. Thirty-eight patients were randomized to receive paclitaxel 175 mg/m² and carboplatin AUC=6 with amifostine 910 mg/m² (group B) or chemotherapy alone (group A). The occurrences of hematologic, neurologic, cardiologic toxicities, and ototoxicity were evaluated. Results: All patients completed the six scheduled cycles of therapy. A total of 114 cycles of chemotherapy was given in both groups. Neutropenia grade 3–4 was observed in 11 cycles (9.6%) in group A and 19 cycles (16.6%) in group B (p=0.16). Paresthesia grade 1 or 2 was observed in 18 of 19 patients of group A and in 8 of 19 patients of group B, following the sixth cycle of chemotherapy (p=0.018). Two patients of group B and nine patients of group A suffered from sensory motor impairment grade 2 (p=0.029). There was no clinical evidence in any patient for deterioration in cardiac function. Asymptomatic and transient sinus bradycardia or ventricular premature beats developed in four patients. None of the patients reported vertigo, tinnitus, or hearing loss. Conclusion: The addition of the amifostine to the combination of paclitaxel and carboplatin may prevent or reduce the incidence of neurotoxicity in the treatment of NSCLC. Amifostine does not appear to have a preventive role in neutropenia.     

Phase 2 trial of carboplatin,weekly paclitaxel,and biweekly bevacizumab in patients with unresectable stage IV melanoma

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in the growth and metastatic progression of melanoma. Exposure of melanoma cells to chemotherapy induces VEGF overproduction, which in turn may allow melanoma cells to evade cell death and become chemotherapy resistant. Therefore, in patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets VEGF might be able to control tumor growth and progression more effectively than chemotherapy alone. METHODS: A 2‐stage phase 2 clinical trial was conducted in patients with unresectable stage IV (metastatic) melanoma to assess antitumor activity and the toxicity profile of the combination of carboplatin (area under the curve 6 iv on Day 1 of a 28‐day cycle), paclitaxel (80 mg/m² iv on Days 1, 8, and 15), and bevacizumab (10 mg/kg iv on Days 1 and 15). Treatment was continued until progression or intolerable toxicity. RESULTS: Fifty‐three patients (62.3% male) were enrolled. Nine (17%) patients achieved partial remission, and another 30 (57%) achieved stable disease for at least 8 weeks. Median progression‐free survival and median overall survival were 6 months and 12 months, respectively. One patient died after 8 treatment cycles from intracranial hemorrhage into undiagnosed brain metastases. The most common severe (grade ≥3) toxicities were neutropenia (53%), thrombocytopenia (11%), hypertension (9%), and anemia (8%). CONCLUSIONS: This combination of carboplatin, paclitaxel, and bevacizumab appears to be moderately well tolerated and clinically beneficial in patients with metastatic melanoma. Further study of this combination is warranted. Cancer 2009. © 2008 American Cancer Society.     

Weekly dose-dense paclitaxel and carboplatin in recurrent ovarian carcinoma: A phase II trial

PurposeThe aim of this study was to investigate efficacy and toxicity of the dose-dense weekly paclitaxel (T) and carboplatin (C) in the management of platinum-resistant/sensitive recurrent epithelial ovarian cancer (EOC) previously treated with 3 weekly paclitaxel/carboplatin.MethodsThirty two patients with recurrent EOC who had received 3 weekly TC before were enrolled. Nine patients relapsed within 6 months (platinum-resistant), 13 patients relapsed after 12 months (platinum-sensitive) and in 10 patients recurrence occurred between 6 and 12 months (intermediate platinum-sensitive). Weekly (T) at a dose of 80 mg/m², followed by weekly (C) AUC 2 on day 1, 8, and 15 of a 28-day cycle for 6 planned cycles were administrated. End-points were overall response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity.ResultsThe ORR was 62.5%. For the platinum-resistant, intermediate platinum-sensitive and platinum-sensitive patients the ORR was 44.4% (4/9), 60% (6/10) and 76.9% (10/13), respectively, and 1 (11.1%), 2 (20%) and 5 (38.46%) patients, respectively had CR. PFS was 9.1 months (6.13, 9.1 and 12.17 months, for the 3 groups, respectively) (P < 0.001). OS was 14 months (9.17, 15.2, and 19.23 months, for the 3 groups, respectively) (P < 0.001). Treatment-related adverse events were manageable with only 1 patient (3.1%) suffering from grade 4 neutropenia. Grade 3 hematological and non-hematological toxicities were neutropenia in 8 (25%), and peripheral neuropathy in 4 (12.5%) patients, respectively.ConclusionWeekly TC is active and well-tolerated in platinum-resistant and platinum-sensitive patients with recurrent EOC previously treated with TC given every 3 weeks.     

A phase II study of bortezomib in the treatment of metastatic malignant melanoma

BACKGROUND: Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti-melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma. METHODS: Patients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a 1.5-mg/m2 intravenous bolus twice weekly for 2 of every 3 weeks). Eligible patients were age > or = 18 years with an Eastern Cooperative Oncology Group performance status of 0-1. The primary goal of the current study was to evaluate the 18-week disease progression-free survival rate and tolerability of bortezomib in these patients. RESULTS: The current study was intended to treat 45 patients. It was closed at the planned interim analysis due to early evidence of insufficient clinical efficacy. Twenty-seven patients with a median age of 56 years (range, 32-77 years)were accrued. There were no major clinical responses to treatment. Only 6 patients (22%) achieved stable disease. Of these 6 patients, 4 were still stable after 4 cycles of treatment, but were removed from the study due to toxicity. The median time to disease progression was 1.5 months (95% confidence interval [95% CI], 1.4-1.6) with a median overall survival of 14.5 months (95% CI, 9-22). Having failed bortezomib, most patients proceeded to other clinical trials. Twenty-six patients were evaluable for toxicity. One patient was removed from the study for other reasons and could not return for the cycle evaluation and thus was never evaluated. Of the 26 patients, no Grade 4/5 treatment-related toxicities (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) were reported. Eleven patients (42%) had Grade 3 toxicities (believed to be at least possibly related to treatment), including sensory neuropathy, thrombocytopenia, constipation, fatigue, ileus, abdominal pain, and infection without neutropenia. The median number of treatment cycles patients received was two (range, one to six treatment cycles). Two patients (7%) had 1 dose delay and 6 patients (22%) had dose reductions during 1 treatment cycle due to adverse events. CONCLUSIONS: Single-agent bortezomib, administered twice weekly x 2 weeks, every 3 weeks at a dose of 1.5 mg/m2, was not found to be effective in the treatment of patients with metastatic melanoma.