Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.     

Phase II study of irinotecan and carboplatin in patients with the refractory or relapsed small cell lung cancer

We examined the safety and efficacy of the combination of irinotecan plus carboplatin in patients with refractory or relapsed small cell lung cancer (SCLC). Patients with previously treated SCLC were eligible. Patients were treated every 3 weeks with carboplatin (with a target area under the concentration versus time curve of 5 mg min/ml using the Calvert formula on day 1) plus irinotecan (50 mg/m² on days 1 and 8). From May 2000 to January 2002, 24 patients were eligible. None of the 22 patients achieved a complete response, but 15 achieved a partial response with an overall response rate of 68.2% (95% confidence interval, 45.1–86.1%). In 13 patients with sensitive disease, the response rate was 92.3% (95% confidence interval, 64.0–99.8%). The median survival time (MST) was 194 days (range 27–605 days). The MST did not differ significantly between patients with sensitive disease (245 days) and those with refractory disease (194 days, P=0.88). One patient died of treatment-related sepsis. Grade 3–4 hematologic toxicities included leukopenia in 58% of patients, neutropenia in 63%, thrombocytopenia in 58%, and anemia in 67%. Grade 3 diarrhea developed in 21% of patients and grade 3–4 infection in 13%. No patients had grade 4 diarrhea or grade 3–4 nausea and vomiting. This regimen is effective and well tolerated in patients with relapsed or refractory SCLC. However, the search for even more active regimens should be continued.     

Weekly administration of irinotecan (CPT-11) plus cisplatin for refractory or relapsed small cell lung cancer

PURPOSE: Weekly administrations of CPT-11 plus cisplatin together with an anti-diarrheal program, the Oral Alkalization and Control of Defecation [Int J Cancer 1999;83:491; Int J Cancer 2001;92:269; Cancer Res 2002;62:179], were evaluated in this phase II study for patients with refractory or relapsed small cell lung cancer. METHODS: Patients were treated by weekly administrations of 60 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin on Days 1, 8 and 15 over 4 weeks. Coinciding with the infusions and for 4 days thereafter, the anti-diarrheal program was practiced using orally administered sodium bicarbonate, magnesium oxide and basic water. RESULTS: Twenty-five patients who had prior treatments of etoposide and platinum containing regimens (16 refractory patients and nine relapsed patients) were entered. The mean dose-intensities of CPT-11 and cisplatin were 154.8 and 77.4 mg/m(2) per course, respectively. Therefore, 86% of the planned dose was delivered. There were 20 partial responses and an overall response rate of 80% (95% confidence interval, 62-96%) was obtained. The median time to progression and the median survival after starting this regimen were 3.6 and 7.9 months, respectively. The major toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 24 and 12% of patients, respectively. One patient with febrile neutropenia was experienced, and Grade 3 diarrhea was observed in 8%. But there was no treatment death. CONCLUSION: Weekly administrations of CPT-11 plus cisplatin together with Oral Alkalization and Control of Defecation provide a practical and well tolerated regimen that was active for refractory or relapsed small cell lung cancer.     

Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004)

PURPOSE: This Phase II trial was designed to determine the response rate, survival, failure-free survival, and toxicity of second-line therapy with karenitecin in patients with relapsed or refractory non-small cell lung cancer (NSCLC). METHODS: Eligibility criteria included: only one prior chemotherapy program, measurable disease, performance status 0-1, adequate hematologic, renal, and hepatic function. Cases were stratified as relapsed or refractory. RESULTS: Fifty-five patients were accrued and 52 were eligible of whom 28 had relapsed and 24 had refractory disease. Overall patient characteristics were: median age 63 years (range, 45-79 years), 52% males, 63% performance status 1, 50% adenocarcinoma, 21% squamous, 15% large cell, and 12% undifferentiated NSCLC. In both strata, one patient each (4%) had a partial response and 12 patients each (43% for relapsed, 50% for refractory) had stable disease. Median survival was 10.4 months (95% CI, 8.5-17.0) for relapsed NSCLC and 6.0 months (95% CI, 3.7-9.7) for refractory NSCLC. One-year survival was 36% (95% CI, 14-58%) and 21% (95% CI, 5-37%) for relapsed and refractory NSCLC, respectively. Frequent toxicities were neutropenia (grade 3/4 in 15/15%) and thrombocytopenia (grade 3/4 in 17/8%). No patient had lethal toxicity. CONCLUSION: Second-line treatment with karenitecin was tolerable with reversible bone marrow suppression as the major toxicity. The partial response rates, median survival times, and 1-year survival rates in the relapsed and refractory subgroups are comparable to overall second-line outcomes for other agents considered active in this clinical setting.     

Phase II study of biweekly administration of docetaxel and irinotecan in patients with refractory or relapsed advanced non-small cell lung cancer

We examined the safety and efficacy of the combination of docetaxel and irinotecan administered biweekly in patients with refractory or relapsed advanced non-small cell lung cancer (NSCLC). Patients with previously treated NSCLC of stage III or IV were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function. From May 2003 through February 2006, 35 patients (27 men and 8 women; median age 64 years; age range 41–75 years) were enrolled. Patients were treated every 4 weeks with docetaxel (33 mg/m² on days 2 and 16) plus irinotecan (50 mg/m² on days 1 and 15). None of the 35 patients achieved a complete response, but five achieved a partial response, for an overall response rate of 14.3% (95% confidence interval, 4.8–30.3%). The median survival time was 8 months (range 2–29 months). The median time to progression was 3 months (range 1–12 months). Grade 3 to 4 hematologic toxicities included leukopenia in 48.6% of patients, neutropenia in 54.3%, and anemia in 25.7%. No patients had grade 3 to 4 diarrhea or nausea and vomiting. Although one patient had grade 3 drug-induced interstitial pneumonia, all side effects were manageable, and there were no treatment-related deaths. In conclusion, the combination of docetaxel and irinotecan administered biweekly is a safe and effective treatment for refractory or relapsed NSCLC. However, the search for even more active regimens should be continued.     

Docetaxel and cisplatin as second-line chemotherapy for advanced non-small cell lung cancer

AIMS AND BACKGROUND: Docetaxel and cisplatin are both active against non-small cell lung cancer (NSCLC). This pilot study evaluated the efficacy and toxicity of docetaxel and cisplatin as second-line chemotherapy for patients with advanced NSCLC. PATIENTS AND METHODS: Eleven patients with advanced NSCLC who had no response to platinum-based treatment or had recurrence after a partial response were enrolled (2 stage III B, 9 stage IV; 8 men, 3 women). Median age was 58 years (range, 40 to 74 years). Seven patients had an Eastern Cooperative Oncology Group performance status of 0, and four had a performance status of 1. Four weeks or more after the end of previous therapy, all 11 patients received docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 every four weeks. RESULTS: Two patients (18.2%) achieved a partial response,five (45.4%) patients had stable disease, and four (36.4%) patients showed progressive disease after initiation of second-line therapy. Median survival was 277 days. Median time to disease progression was 101 days, and the one-year survival rate was 36.4%. Hematological toxicities were moderate. Grade 3 and 4 leukocytopenia and neutropenia were observed in five (45.4%) patients. Grade 3 anemia occurred in one (9 .1%) patient. No severe non-hematological toxicities were observed except grade 3 nausea in two (18.2%) patients. CONCLUSIONS: The regimen of docetaxel and cisplatin has reasonable efficacy with moderate toxicity as second-line chemotherapy for patients with previously treated, advanced NSCLC.     

Cisplatin schedule in combination with gemcitabine in unresectable non-small cell lung cancer

Gemcitabine (on days 1, 8, and 15)-cisplatin (on day 15) combinations were used to treat 9 patients with unresectable non-small cell lung cancer to study efficacy and safety. Gemcitabine 1,000 mg/m2 was administered on days 1, 8, and 15 of a 28-day cycle. Cisplatin 60-65 mg/m2 was administered on day 15 of a 28-day cycle. Three cycles were planned per patient. The nine patients received 25 cycles of chemotherapy. Objective response rates was 55% (complete response 11% and partial response 44%). Stable disease was 33%, and progressive disease was 11%. Seven of 9 patients received the planned 3 cycles of therapy. Two patients received only 2 cycles, due to progressive disease (1 patient), and ulcerative colitis (1 patient). Grade 3 leukopenia was 22%, and grade 3 neutropenia was 11%. No grade 4 hematological toxicities were observed. Grade 3 anorexia was 11%, and grade 3 skin rash which occurred in the first cycle 22%. Our data show less toxicity and no significant difference in response rates, so the administration of cisplatin on day 15 seemed to be a useful and safe regimen.     

每周低剂量长春瑞滨、顺铂同步后程适形放射治疗局部晚期非小细胞肺癌的Ⅱ期临床研究

目的：探讨每周低剂量长春瑞滨（NVB）、顺铂（PDD）同步后程适形放射治疗局部晚期非小细胞肺癌（NSCLC）的可行性及观察其近期疗效和毒副反应。方法：首程经病理确诊的21例局部晚期NSCLC（根据UICC1997分期标准ⅢA期8例，ⅢB期13例）患者，符合KPS≥70分，年龄≤70岁，近3月体重下降≤5％，器官功能正常。全部患者均行每周1次低剂量NP方案（NVB12．5mg／m^2，PDD20mg／m^2）化疗，共7～9次。每周化疗结束后立即行放疗，先期同步常规放疗38Gy／19F，继之适形放疗推量至60～64Gy／6～7周；锁骨上区照射者推量至60Gy。结果：21例全部完成治疗计划，可行疗效评估，肺原发灶完全缓解（CR）14、3％（3／21），部分缓解（PR）61、9％（13／21），无变化和进展（NC＋PD）22．8％（5／21），总有效率（CR＋PR）为76．2％（16／21）。1年和2年生存率分别为76．2％、40、8％。3～4级白细胞减少发生率为33．3％（7／21）；3级血小板减少发生率为4．8％（1／21）；3级放射性食管炎9．6％（2／21）；无3级及以上放射性肺炎的发生。加用糖皮质激素后症状及影像学表现均好转，无治疗相关性死亡。结论：同期化疗加适形放疗治疗局部晚期NSCLC能为绝大多数患者耐受，有较好的近期疗效，值得临床进一步研究。     

Bortezomib,doxorubicin and dexamethasone in advanced multiple myeloma

BackgroundBortezomib has shown significant activity in myeloma. In this multicenter trial, we assessed for the first time the combination of bortezomib, doxorubicin and low-dose dexamethasone (PAd) in the treatment of relapsed/refractory myeloma.Patients and methodsSixty-four patients were treated for a median of four 28-day cycles (1–6). Bortezomib was given at 1.3 mg/m² (days 1, 4, 8, 11) and dexamethasone at 40 mg (days 1–4); 34 patients receive doxorubicin at 20 mg/m² (days 1, 4) while 30 patients pegylated liposomal doxorubicin at 30 mg/m² (day 1).ResultsFifty-eight percent of patients had undergone prior autologous transplantation, 70% prior anthracycline and 27% prior bortezomib-based regimens. Forty-three patients (67%) achieved at least a partial response including 16 (25%) with at least a very good partial response. One-year event-free survival was 34% after PAd and 31% after the previous line of therapy (hazard ratio 1.20, 95% confidence interval 0.76–1.90, P = 0.43). One-year overall survival from the start of PAd was 66%. Grade 3–4 toxic effects included thrombocytopenia (48%), neutropenia (36%), infections (15%), anemia (13%), gastrointestinal disturbances (11%) and peripheral neuropathy (10%). Two patients had grade 3–4 cardiac heart failure.ConclusionsPAd is an active salvage therapy with manageable toxicity in patients with relapsed/refractory myeloma.     

Efficacy and safety of amurubicin for the elderly patients with refractory relapsed small cell lung cancer as third-line chemotherapy

Background: While more elderly patients are being diagnosed with lung cancer every year, no anti-lung cancer therapy designed specifically for the elderly has been established yet. This is the first retrospective study to examine the efficacy and safety of amurubicin (AMR) for elderly patients with refractory relapsed small cell lung cancer (SCLC) as second or third-line chemotherapy. Materials and Methods: Thirty-six patients were eligible for analyzing the frequency of hematologic and non-hematologic toxicities and effectiveness of AMR for refractory relapsed SCLC in both elderly (≥70 years) and non-elderly (<70 years) groups. Results: Among these patients as third-line chemotherapy, the response rate and the disease control rate of refractory relapsed cases were 44.4 and 55.6%, respectively. The median of progression-free survival time was 3.0 months and the median of overall survival time was 5.1 months. There were no significant differences in the frequency of the grade 3-5 hematologic or non-hematologic toxicity between the elderly (≥70 years) and non-elderly (<70 years) patients or second and third-line chemotherapies. Conclusions: AMR could be one of the effective tools in the treatment of elderly patients with refractory relapsed SCLC as third-line chemotherapy, and the recommended dose is 30 mg/m 2 for three consecutive days.     

CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To evaluate the activity of CPT-11, which is a new derivative of camptothecin, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Sixteen patients with refractory or relapsed SCLC were entered onto a prospective, non-randomized, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Five patients had received previous chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide (CODE) as an induction therapy. Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous (IV) infusion every week with subsequent doses based on toxicity. Fifteen patients were assessable for toxicity, response, and survival. RESULTS: Seven patients (47%; 95% confidence limits for an overall response rate, 21.4% to 71.9%) responded to CPT-11 with a median duration of response of 58 days. The major toxicities were myelosuppression (predominantly leukopenia), diarrhea, and pulmonary toxicity. CONCLUSION: CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SCLC.     

Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study.

BACKGROUND: To investigate the efficacy and toxicity of the combination of gemcitabine and oxaliplatin (GEMOX) in patients with relapsed or cisplatin-refractory non-seminomatous germ cell tumors (NSGCT). PATIENTS AND METHODS: Twenty-nine patients with relapsed or cisplatin-refractory NSGCT were treated with gemcitabine 1000 mg/m2 on days 1 and 8 followed by oxaliplatin 130 mg/m2 on day 1 every 3 weeks for a maximum of six cycles. Twenty-four patients (83%) were considered refractory and five (17%) absolutely refractory to cisplatin. RESULTS: Twenty-eight patients were assessable for response. Overall, nine patients (32%) achieved a favourable response (complete response, four; partial response, five). One of the complete responders relapsed after 7 months and went into disease-free status lasting for 11+ months after resection of lung metastases. The rest of the complete responders are continuously disease-free at 14+, 19+ and 28+ months with the study regimen plus or minus surgery. One of the complete responders had absolutely cisplatin-refractory disease and another one presented with a late relapse. Toxicity was primarily hematological and generally manageable: 62% of patients experienced grade 3/4 neutropenia, 10% neutropenic fever and 41% grade 3/4 thrombocytopenia. Non-hematological toxicity consisted mainly of nausea/vomiting. Three patients (10%) developed grade 3 neurotoxicity and discontinued treatment. CONCLUSIONS: The combination of GEMOX is an active, moderately toxic and easily administered regimen in patients with relapsed or cisplatin-refractory NSGCT. The 14% long-term disease-free status accomplished in this heavily pretreated patient population is quite encouraging.     

Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study

The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in 54 chemotherapy-naive patients with metastatic non-small cell lung cancer (NSCLC). Gemcitabine i.v. 1000 mg/m(2)was administered on days 1 and 8 and paclitaxel 200 mg/m(2)as a continuous 3-hour infusion on day 1. Treatment was repeated every 21 days. Patients had a median age of 53 years. ECOG performance status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved a complete response and 15 (31.9%) achieved a partial response giving an overall response rate of 36.2% (95% CI: 22.4-49.9%); 19 patients (40.4%) had stable disease and 10 (21.3%) had progressive disease. The median survival time was 51 weeks (95% CI: 46.5-59.3), with a 1-year survival probability of 0.48 (95% CI: 0.34-0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and 2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade 1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or 2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%) and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an active and well-tolerated regimen for the treatment of advanced NSCLC, and warrants further investigation in comparative, randomized trials.     

Combination of irinotecan hydrochloride and etoposide for treatment of refractory or relapsed small-cell lung cancer

We used a combination of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor as a support therapy for refractory or relapsed small-cell lung cancer (SCLC). This combination regimen was active against refractory or relapsed SCLC as gauged by a response rate of 71% and a median survival time of 271 days. Further studies of this combination regimen in refractory or relapsed SCLC are warranted.     

Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom's macroglobulinemia: results of WMCTG Trial 03-248.

PURPOSE: Waldenstrom's macroglobulinemia (WM) is a B-cell disorder. Despite advances in the therapy, WM remains incurable. As such, novel therapeutic agents are needed for the treatment of WM. EXPERIMENTAL DESIGN: In this multicenter study, 27 patients with WM received up to eight cycles of bortezomib at 1.3 mg/m(2) on days 1, 4, 8, and 11. All but one patient had relapsed/or refractory disease. RESULTS: Following therapy, median serum IgM levels declined from 4,660 to 2,092 mg/dL (P < 0.0001). The overall response rate was 85%, with 10 and 13 patients achieving minor and major responses, respectively. Responses were prompt and occurred at median of 1.4 months. The median time to progression for all responding patients was 7.9 (range, 3-21.4+) months. The most common grade III/IV toxicities occurring in > or =5% of patients were sensory neuropathies (22.2%), leukopenia (18.5%), neutropenia (14.8%), dizziness (11.1%), and thrombocytopenia (7.4%). Sensory neuropathies resolved or improved in nearly all patients following cessation of therapy. CONCLUSIONS: The results of these studies show that bortezomib is an active agent in relapsed and refractory WM.     

Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma

BACKGROUND: Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma. METHODS: Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS: Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently. CONCLUSIONS: Retreatment with or continuation of bortezomib +/- dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.     

Single-agent irinotecan as second-line treatment for advanced gastric cancer

AIM: To investigate the activity and toxicity of irinotecan (CPT-11) as a single agent in patients with advanced gastric cancer after failure of previous 5-fluorouracil-based combination chemotherapy. PATIENTS AND METHODS: Sixteen patients with advanced gastric received CPT-11, 350 mg/m2 every 21 days. The median age of the patients was 54.6 years; ECOG performance status was 0-1 in 14 patients and 2 in 2 patients. Dominant metastatic sites included liver, lung, lymph nodes and peritoneum. RESULTS: No complete response was observed. Two patients (12.5%) achieved a partial response to treatment. One patient (6.25%) had a minor response. Ten patients (62.5%) had progressive disease on therapy, and 3 patients (18.75%) had stable disease. The median survival of all 16 patients was 5 months. Grade 3 neutropenia was observed in 3 patients (18.75%), grade 4 thrombocytopenia in 1 patient (6.25%), and grade 3 anemia in 1 patient (6.25%). Three patients (18.75%) suffered from grade 3 diarrhea. CONCLUSIONS: CPT-11 is moderately active and a well-tolerated regimen for selected advanced gastric cancer patients who experience disease progression after receiving first-line treatment.     

Gemcitabine plus paclitaxel as first-line chemotherapy for patients with advanced breast cancer

OBJECTIVES: To assess the efficacy and tolerability of gemcitabine and paclitaxel as first-line treatment in advanced breast cancer. METHODS: Patients with histologically confirmed metastatic or metastatic plus locally advanced breast cancer received gemcitabine 1,200 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days for 8 cycles. RESULTS: From December 1999 to August 2001, 45 patients, with a median age of 53.5 years (range, 22-77), received a total of 260 cycles. All were assessable for response and toxicity. Twenty-seven patients had prior adjuvant therapy. Hormonal receptor status was positive in 31.1% and negative in 40.0% of patients. Main metastatic sites included soft tissue (62.2%) and lung (53.3%). The objective response rate was 66.7%; complete response, 22.2%; partial response, 44.4%; stable disease, 15.6%; progressive disease, 17.8%. Median duration of response was 18 months and median time to tumor progression was 11 months. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia developed in 13.3% of patients, and 15.5% developed grade 3/4 mucositis. No treatment-related deaths occurred. Median overall survival was 19 months. CONCLUSIONS: Gemcitabine plus paclitaxel is an active combination with a favorable toxicity profile as first-line treatment for patients with advanced breast cancer.     

Phase II trial of gemcitabine/irinotecan in refractory or relapsed small-cell lung cancer

BACKGROUND: Gemcitabine and irinotecan have shown a broad range of activity in solid tumors, including small-cell lung cancer (SCLC), with a synergistic effect on SCLC cell lines. The objective of this phase II trial was to evaluate the activity of gemcitabine/irinotecan in patients with relapsed SCLC. PATIENTS AND METHODS: Thirty-five patients (15 with refractory disease and 20 with sensitive disease) who had experienced treatment failure with 1 previous chemotherapy regimen were recruited. Treatment consisted of gemcitabine 1,000 mg/m(2) and irinotecan 100 mg/m(2) on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and signed informed consent. RESULTS: All 35 patients were assessable for response, survival, and toxicity. Best objective responses exhibited were as follows: complete response in 2 patients (6%), partial response in 4 (11%; 95% confidence interval [CI], 21%-61%), stable disease in 7 (20%; 95% CI, 9%-45%), and progressive disease in 22 (63%; 95% CI, 17%-57%). Median time to disease progression was 3.4 months and median survival was 5.8 months. The 1-year survival rate was 34%. Toxicity was mainly hematologic. Grade 3/4 nausea and vomiting occurred in 9% of patients, neuropathy occurred in 2.8%, and diarrhea occurred in 14.3%. Survival was not significantly different for patients with refractory versus sensitive disease. CONCLUSION: The combination of gemcitabine/irinotecan was shown to be active as second-line chemotherapy, especially in patients with refractory disease.     

Phase II trial of irinotecan/gemcitabine as second-line therapy for relapsed and refractory small-cell lung cancer: Cancer and Leukemia Group B Study 39902.

BACKGROUND: This phase II study evaluated the efficacy and safety of the irinotecan/gemcitabine combination in patients with relapsed/refractory small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with measurable tumor who had received one previous chemotherapy or chemotherapy/radiation regimen were eligible. Gemcitabine 1000 mg/m(2) was administered i.v. over 30 min followed immediately by irinotecan 100 mg/m(2) i.v. over 90 min, both on days 1 and 8 every 21 days. Patients were stratified based on response to initial treatment [i.e. primary sensitive disease with progression >or=3 months (group A), or refractory disease (group B)]. RESULTS: Seventy-three patients were enrolled but one never received treatment and one ineligible patient did not have SCLC. Median patient ages of the remaining patients were 61 and 63 years in groups A (n = 35) and B (n = 36), respectively, with performance status of 0 or 1 in 85% of 71 patients. Primary grade 3/4 toxic effects in groups A versus B were neutropenia (36% versus 43%), thrombocytopenia (36% versus 26%), nausea (12% versus 11%), vomiting (0 versus 11%), diarrhea (12% versus 9%), and pulmonary (12% versus 12%). Two patients had fatal events including pneumonitis (n = 1) and acute respiratory distress syndrome (n = 1). Responses occurred in 11 group A [two complete responses and nine partial responses (PRs)] and four group B (all PRs) patients, for response rates of 31% [95% confidence interval (CI) 17%, 49%) and 11% (95% CI 3%, 26%), respectively. Median survival and progression-free survival times were 7.1 (95% CI 6, 10.5) versus 3.5 (95% CI 3.1, 5.7) months, and 3.1 (95% CI 1.6, 5.3) versus 1.6 (95% CI 1.4, 2.8) months for group A versus B. CONCLUSION: The irinotecan/gemcitabine combination is active and well tolerated as second-line therapy in SCLC patients. Additional studies are warranted as second-line therapy in patients who progressed 90 days or more after first-line therapy. However, the observed efficacy results in refractory SCLC patients indicate that this regimen should not be further explored in this population.