Intravenous carboplatin for recurrent malignant glioma: a phase II study.

Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate.     

A phase II trial of recombinant interferon alpha-2b and cisplatin in metastatic melanoma

In this phase II study 37 patients with metastatic melanoma were treated with cisplatin 100 mg/m2 every three weeks and interferon alpha-2b 10 MU subcutaneously three times weekly; 125 cycles were administered. Thirty-four patients were evaluable for response and all 37 patients were assessable for toxicity. Four patients stopped treatment with cisplatin because of severe nephrotoxicity, and six patients stopped therapy because of other toxicities. Response rate was 6/34 = 18% (95%) CI (confidence interval): 7%-35%). One patient reached complete response lasting 27+ months. Five patients obtained partial responses with a median duration of response of 7 months (range 5-15+ ). Median time to progression was 2.3 months (range 1-27+). Median survival was 5 months (range 1-27+). We conclude that the combination of high-dose cisplatin 100 mg/m2 and interferon alpha-2b is associated with unacceptable toxicity. Haematological toxicity and nephrotoxicity were pronounced and the response rate was meagre and not encouraging.     

Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma. PATIENTS AND METHODS: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy. RESULTS: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy. CONCLUSION: We conclude that further testing of EPI in malignant mesothelioma is warranted.     

Raltitrexed-Oxaliplatin combination chemotherapy is inactive as second-line treatment for malignant pleural mesothelioma patients

Within a single-institution phase II trial, we investigated the antitumor activity of the Raltitrexed-Oxaliplatin combination as second-line therapy for malignant pleural mesothelioma (MPM). Fourteen patients were enrolled and all were assessable for response. The trial was then closed because chemotherapy, though well tolerated, yielded no objective responses. The best response observed was disease stabilization in 4 patients only (28.57%), while the other 10 patients (71.42%) progressed despite treatment. Median time to progression (TTP) was 8 weeks (average: 9.85, range: 7-20), while median overall survival was just 14 weeks (average: 21.69, range: 9-66+).     

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 II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.

BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.     

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP)

BACKGROUND: The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial. METHODS: From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. RESULTS: Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively. CONCLUSIONS: This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.     

Flavopiridol in untreated or relapsed mantle-cell lymphoma: results of a phase II study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the response rate and toxicity of flavopiridol in patients with previously untreated or relapsed mantle-cell lymphoma. PATIENTS AND METHODS: Adult patients with previously untreated or in first or second relapse of previously responsive mantle-cell lymphoma were given flavopiridol 50 mg/m2/d by intravenous bolus for 3 consecutive days every 21 days with antidiarrheal prophylaxis. Flavopiridol was continued until disease progression, unacceptable toxicity, or stable disease for four cycles. Disease was reassessed every two cycles. RESULTS: From 33 registered patients, 30 were eligible after pathology review, 30 were assessable for toxicity, and 28 were assessable for response. A median of four cycles of treatment was administered; 90% of patients received at least 90% of planned dose-intensity. No complete responses were seen; three patients had a partial response (11%), 20 patients had stable disease (71%), and five patients had progressive disease (18%). The median duration of response was 3.3 months (range, 2.8 to 13.2 months). The most common toxicities were diarrhea (97%), fatigue (73%), nausea (47%), and vomiting (27%). At least one nonhematologic grade 3 or 4 toxicity was seen in 14 patients (47%). Hematologic toxicity was modest. CONCLUSIONS: Flavopiridol given as a daily bolus for 3 consecutive days every 3 weeks has modest activity as a single agent for mantle-cell lymphoma. The number of stable and partial responses that was seen indicates that it is biologically active and may delay progression. Future studies in mantle-cell lymphoma should test this agent with other active agents and using different schedules.     

Epirubicin and gemcitabine as first-line treatment in malignant pleural mesothelioma

Malignant pleural mesothelioma represents a rare disease, for which chemotherapy actually remains unsatisfactory. From August 1998 to November 2001, 28 chemo-radio-immunonaive patients were consecutively enrolled in the trial: 22/6 males/females; median age 63 years (range, 45-79); median ECOG PS 1 (range, 0-2). They were treated with epirubicin (100 mg/m2 iv on day 1) plus gemcitabine (1000 mg/m2 iv on days 1 and 8) every 4 weeks for 6 cycles. Patients who responded to chemotherapy (n = 6) were subsequently treated with interleukin-2 (4,500,000 IU) subcutaneously every other day, until progression. A total of 124 epirubicin-gemcitabine cycles were administered (median, 6/patient; range, 2-6). Twenty-six patients were evaluated for toxicity. According to WHO criteria, we observed grade III-IV hematological and gastrointestinal toxicity respectively in 3 patients (11%) and 1 patient (3%). No red cell transfusions were required and no toxic deaths occurred. Two patients (8%) could not be evaluated for response (no therapy performed). According to WHO criteria, the final responses were: partial in 4 patients (14%), stable disease in 19 patients (69%), and progression in 3 patients (10%). In 26 patients, the median survival was 55 weeks (range, 7-222) and median time to progression 30 weeks (range, 4-156). At the time of this writing, no patient is alive. The 1-year survival was 32%, 2-year survival 11%, and 4% at 3 and 4 years. All patients were at stage III, and time to progression was 58 weeks and survival 63.5 weeks, without any toxicity. This multi-center phase II clinical trial showed that epirubicin plus gemcitabine, as a first-line treatment in malignant pleural mesothelioma, has promising activity with a good tolerability profile and symptom palliation. The role of interleukin-2 in maintenance therapy for malignant pleural mesothelioma is encouraging and requires further study.     

Multicenter phase I/II study of cetuximab with paclitaxel and carboplatin in untreated patients with stage IV non-small-cell lung cancer.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have demonstrated antitumor activity in patients with non-small-cell lung cancer (NSCLC). This study examined the safety profile of the monoclonal antibody EGFR inhibitor, cetuximab, when added to paclitaxel and carboplatin in untreated patients with stage IV NSCLC. Secondary objectives included efficacy and paclitaxel and carboplatin pharmacokinetics during cetuximab treatment. PATIENTS AND METHODS: Patients with tumor evidence of EGFR by immunohistochemistry, performance status of 0 to 2, and measurable disease received paclitaxel 225 mg/m2 with carboplatin area under the curve = 6 on day 1 every 3 weeks. Cetuximab was administered at 400 mg/m2, 1 week before paclitaxel and carboplatin, then weekly at 250 mg/m2. The regimen continued until disease progression or intolerable toxicity. RESULTS: Thirty-one of 32 enrolled patients were treated. The most common cetuximab toxicity was rash in 84% of patients (grade 3 in 13%). Pharmacokinetic sampling did not reveal an interaction between carboplatin, paclitaxel, and cetuximab. An objective response was observed in eight patients (26%). With a median follow-up of 19 months, the median time to progression was 5 months, median survival was 11 months, and the 1- and 2-year survival rates were 40% and 16%, respectively. CONCLUSION: The combination of cetuximab, paclitaxel, and carboplatin was safe and well tolerated in this population of stage IV patients. The response rate, time to progression, and median survival were slightly superior to historical controls treated with paclitaxel and carboplatin alone. A randomized phase II trial has completed accrual.     

Final results of a phase II clinical trial of weekly docetaxel in combination with capecitabine in anthracycline-pretreated metastatic breast cancer

The addition of capecitabine to docetaxel on a 3-week schedule resulted in superior response rate, increased time to progression (TTP), and improved overall survival in patients with anthracycline-pretreated metastatic breast cancer (MBC). Because the toxicity profile of weekly docetaxel differs from the standard 21-day docetaxel schedule, we performed a phase I/II trial to test the efficacy and safety of weekly docetaxel in combination with capecitabine given for 14 days every 21 days. The phase I study identified the doses of docetaxel (30 mg/m2 weekly) and capecitabine (900 mg/m2 twice daily on days 1-14 every 21 days) used in phase II. Twenty female patients with measurable or assessable MBC were enrolled. Eighteen patients had previously received anthracyclines; 2 had contraindications to anthracyclines. Patients remained on study for a maximum of eight 3-week cycles or until tumor progression or unacceptable toxicity occurred; response assessments were scheduled after cycle 2, 5, and 8. Seventeen patients were assessed after cycle 2; 3 subjects (18%) had a partial response (PR), 9 had stable disease (53%; SD), and 5 patients (29%) had progressive disease (PD). Ten patients were assessable after cycle 5. Two patients (20%) had a PR, 5 patients (50%) had SD, and 3 patients (30%) had PD. The most common grade 3 toxicities were nail loss (45%), asthenia (30%), and hand-foot syndrome (30%), and toxicities led to study discontinuation in 10 patients. The median time to treatment failure was 10 weeks and median TTP was 26 weeks. The median duration of response was 9 weeks and the median duration of SD was 16 weeks. The median overall survival was 82 weeks. This schedule of weekly docetaxel in combination with day 1-14 capecitabine has activity; however, toxicity discourages the use of this schedule in lieu of the standard docetaxel/capecitabine regimen.     

5-fluorouracil-carboplatin continuous infusion as salvage chemotherapy in advanced cancer

AIMS AND BACKGROUND: 5-fluorouracil given by continuous infusion allows higher dose delivery, causes less myelosuppression and may interfere with repair of DNA damage caused by carboplatin. With this rationale, we conducted a phase II study to test the activity and toxicity of 5-fluorouracil and carboplatin given in continuous infusion to patients with advanced cancer and pretreated with at least two chemotherapy regimens. METHODS: Forty patients with advanced tumors (21 colon, 4 stomach, 3 breast, 3 bladder, 3 ovary, and 6 at other sites) were entered in the trial. 5-fluorouracil (200 mg/m2) and carboplatin (20 mg/m2) were administered by continuous infusion from days 1 to 20, every 4 weeks. RESULTS: All patients were assessable for response and toxicity. A total of 138 courses of chemotherapy were administered, with a mean of 3.5 per patient (range, 2-9). Toxicity, assessed using WHO criteria, was as follows: nausea and vomiting grade 2-3 in 34% of patients, alopecia grade 2-3 in 96%, and neutropenia grade 3-4 in 26%. One patient (2.5%) had a complete response to therapy and 7 (17.5%) had a partial response (response rate 20%; 95% Cl, 9.06-35.68%). Disease stability and progression occurred in 12 (30%) and 20 (50%) patients, respectively. Median time to progression was 5.6 months (range, 2.8-45.9+), with a median survival time of 7.7 months (range, 1.5-45.9+). CONCLUSIONS: Outpatient treatment with a combination of 5-fluorouracil and carboplatin in continuous infusion was active as salvage treatment for advanced tumors and may give prolonged palliation of symptoms with manageable toxicity.     

Phase II trial of daily low-dose carboplatin and thoracic radiotherapy in elderly patients with locally advanced non-small cell lung cancer

BACKGROUND: The purpose of this study was to investigate the feasibility of concurrent thoracic radiotherapy (TRT) and daily low-dose carboplatin (CBDCA) in elderly patients with locally advanced non-small cell lung cancer (NSCLC) and to estimate tumor response, toxicity and survival. METHODS: Forty patients were entered in a multicenter phase II study. All were patients with pathologically documented unresectable stage IIIA or IIIB or medically inoperable stage I, II NSCLC. CBDCA 30 mg/m2 was given on days 1-5 in weeks 1-4 concurrently with TRT, mainly for radiosensitization. TRT was started 1 h after CBDCA (30 min infusion) was given. TRT was given in 2 Gy/fraction/day, 5 days a week for a total of 50-60Gy. RESULTS: Thirty-eight patients were assessable for treatment response and toxicity. One patient had a CR and 18 patients PRs with a response rate of 50% (95% CI, 33.4-66.6%). The main toxicities were hematological toxicity. Other toxicities were grade > or =2 esophagitis in one patient, grade 3 nausea/vomiting in one and grade > or =3 pulmonary toxicity in two. There was one treatment-related death due to pulmonary toxicity. For stage IIIA + IIIB patients, the median survival time was 15.1 months and 1-and 2-year actuarial survival rates were 52.6 and 20.5%, respectively. For stage I + II patients, 1- and 3-year actuarial survival rates were 90.9 and 69.3%, respectively. CONCLUSIONS: The data suggest that TRT with daily low-dose CBDCA in elderly patients is effective and feasible because of its low toxicity and survival.     

Treatment of recurrent malignant supratentorial gliomas with carboplatin (CBDCA)

Summary Twenty patients with malignant supratentorial gliomas progressing after radiation therapy and chemotherapy with nitrosoureas received intravenous carboplatin, 450 mg/m². Courses of therapy were repeated every four weeks. Therapeutic evaluation was performed monthly using neurologic examination and CT scan of the brain. Of 19 patients evaluable for response, 2 (10%) responded to therapy and 6 (30%) had stable disease. The estimated median time to tumor progression for responding and stable patients was 6 months. Median duration of survival was 6 months for all patients. Of 20 patients evaluable for toxicity, none had renal or auditory toxicity. Side effects consisted of hematologic toxicity in 4 patients (20%): one patient had grade 4 toxicity requiring discontinuation of carboplatin and 3 patients had grade 2–3 toxicity.Abbreviation HECNU 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea     

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.     

紫杉醇联合卡铂与氟尿嘧啶联合卡铂治疗艾滋病并发晚期阴茎癌的临床对比分析

目的比较紫杉醇联合卡铂与5-氟尿嘧啶（5-Fu）联合卡铂治疗艾滋病并发晚期阴茎癌患者临床疗效、不良反应及预后。方法选择经病理或细胞学以及血清学证实的58例艾滋病并发晚期阴茎癌患者,其中30例接受紫杉醇联合卡铂方案化疗（TC组）,28例接受5-Fu联合卡铂方案化疗（FC组）,按实体瘤的疗效评价标准(RECIST)1.0版评价近期疗效,按美国癌症研究所常见毒性判定标准（NCI-CTC）3.0版评价不良反应。结果58例均可评估疗效,TC组和FC组的客观总有效率分别为56.7%和17.9%（χ²=9.265,P=0.002）,中位疾病进展时间分别为11.15月和7.22月（χ²=6.737,P=0.009）,中位生存时间分别为17.36月和9.11月（χ²=10.646,P=0.001）。两组主要不良反应均为骨髓抑制及恶心呕吐,Ⅲ～Ⅳ度白细胞减少发生率分别为46.4%和40.0%（χ²=0.222,P=0.637）,Ⅲ～Ⅳ度恶心呕吐的发生率分别为36.0%和34.78%（χ²=0.008,P=0.930）。结论紫杉醇联合卡铂化疗方案治疗艾滋病并发晚期阴茎癌是安全和有效的。     

Second-line,low-dose,weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line chemotherapy with carboplatin plus paclitaxel

BACKGROUND: Second-line chemotherapy with docetaxel improves survival and quality of life (QoL) in patients with nonsmall cell lung carcinoma (NSCLC) who fail first-line platinum-based regimens. The authors sought to determine the activity of second-line, low-dose, weekly paclitaxel in patients with NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. METHODS: Patients with Stage IIIB/IV NSCLC who had received first-line carboplatin/paclitaxel were treated with low-dose (80 mg/m(2)), weekly paclitaxel at the time of disease progression. Response rates, QoL, and survival were outcome end points. RESULTS: Sixty-two patients were included in this analysis. The median age was 62 years (range, 32-76 years), 55% of patients were male, 89% of patients had Stage IV NSCLC, and the Karnofsky performance status was 90-100% in 31% of patients, 70-80% in 55% of patients, and 60% in 14% of patients. Twenty-six percent of patients experienced disease progression as their best response to first-line carboplatin plus paclitaxel, whereas 52% of patients had stable disease, and 23% of patients had achieved a response. The median time from first-line carboplatin plus paclitaxel to second-line, low-dose, weekly paclitaxel was 9.5 weeks (range, 1-78 weeks). The toxicity profile was extremely favorable, with no Grade 4 toxicity and < 10% Grade 3 hematologic or nonhematologic toxicity in all patients with the exception of neuropathy. Ten percent of patients experienced both Grade 2 and Grade 3 neuropathy. The overall objective response rate was 8%. The median survival was 5.2 months (95% confidence interval [95%CI], 3.6-6.2 months), and the 1-year and 2-year survival rates were 20% (95%CI, 10-30%) and 9% (95%CI, 1-16%), respectively. CONCLUSIONS: Second-line, low-dose, weekly paclitaxel had activity in selected patients with Stage IIIB/IV NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. The toxicity profile of this approach is extremely favorable, and outcome expectations are similar to the outcome expectations with other single agents in this setting.     

Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin/paclitaxel in patients with early-stage (I/II) non-small-cell lung cancer: long-term results of a phase II study.

PURPOSE: Feasibility and activity of concurrent hyperfractionated radiotherapy (Hfx RT) and low-dose, daily carboplatin and paclitaxel were investigated in patients with early-stage (I/II) non-small-cell lung cancer in a phase II study. PATIENTS AND METHODS: Fifty-six patients started their treatment on day 1 with 30 mg/m2 of paclitaxel. Hfx RT using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent low-dose daily carboplatin 25 mg/m2 and paclitaxel 10 mg/m2, both given Mondays through Fridays during the RT course, started from the second day. RESULTS: There were 29 complete responses (52%) and 15 partial responses (27%), and 12 patients (21%), experienced stable disease. The median survival time was 35 months, and 3- and 5-year survival rates were 50% and 36%, respectively. The median time to local progression has not been achieved, but 3- and 5-year local progression-free survival rates were 56% and 54%, respectively. The median time to distant metastasis has not been achieved, but 3- and 5- year distant metastasis-free survival rates were 61% and 61%, respectively. The median and 5-year cause-specific survivals were 39 months and 43%, respectively. Acute high-grade (> 3) toxicity was hematologic (22%), esophageal (7%), or bronchopulmonary (7%). No grade 5 toxicity was observed. Late high-grade toxicity was rarely observed (total, 10%). CONCLUSION: Hfx RT and concurrent low-dose daily carboplatin/paclitaxel was feasible with low toxicity and effective in patients with stage I/II non-small-cell lung cancer. It should continue to be investigated for this disease.     

A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma: a North Central Cancer Treatment Study, N0021

BACKGROUND: The North Central Cancer Treatment Group (NCCTG) conducted a phase 2 study to evaluate the antitumor activity of the combination of gemcitabine and epirubicin in patients with pleural mesothelioma who received no more than 1 prior chemotherapy regimen. METHODS: A total of 23 patients were accrued between August 2001 and April 2002 and received gemcitabine at a dose of 1000 mg/m(2) intravenously over 30 minutes weekly every 2 weeks and epirubicin at a dose of 90 mg/m(2) intravenously on Day 1 on an every-21-days cycle (high-dose patient group). Between August 2002 and April 2004, an additional 45 patients were treated at a reduced dose of gemcitabine of 750 mg/m(2) and epirubicin at a dose of 70 mg/m(2) with the same schedule (low-dose patient group). RESULTS: In the high-dose patient group, the confirmed response rate was 13% (95% confidence interval [95% CI], 3-34%). The median survival was 9.3 months (95% CI, 7.4-10.7 months) and the median time to disease progression was 6.3 months (95% CI, 3.0-7.6 months). In the low-dose patient group, the confirmed response rate was 7% (95% CI, 0-28%). The median survival was 5.7 months (95% CI, 4.7-8.7 months) and the median time to disease progression was 4.2 months (95% CI, 2.7-5.6 months). Toxicity was moderate to severe. In the high-dose and low-dose groups, 87% and 60% of patients, respectively, experienced at least 1 adverse event of grade 4 or higher (according to National Cancer Institute Common Toxicity Criteria [version 2.0]). The quality of life remained similar from baseline to the end of the 2 cycles of treatment in the high-dose group but worsened in the low-dose group. CONCLUSIONS: In the current study, the combination regimen of gemcitabine and epirubicin was found to demonstrate minimal antitumor activity against pleural mesothelioma.     

Phase II trial of recombinant tumor necrosis factor in disseminated malignant melanoma.

Twenty-one patients with disseminated malignant melanoma received recombinant tumor necrosis factor (TNF), 150 micrograms/m2 intravenously on days 1-5 every 2 weeks for four cycles and then every 3 weeks. Recombinant TNF produced no meaningful palliation. One patient (5%) attained an objective response of nodal, but not visceral, disease, which lasted 3 weeks. The median time to progression was 4 weeks. The median survival was 7.7 months. Ninety percent of patients developed mild to severe cytokine "flu." Ten percent developed significant hepatic toxicity (AST greater than 3 times normal). As a single agent, recombinant TNF is not likely to palliate disseminated malignant melanoma. However, combinations of recombinant TNF and cytotoxic or immune modulatory agents, particularly gamma interferon, may merit further investigation.