Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-na?ve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.     

Cisplatin and etoposide (VP-16) as a single regimen for small cell lung cancer. A phase II trial

Forty-seven consecutive patients with small cell lung cancer (SCLC) were treated with a combination chemotherapy program including 60 mg/m2 of cisplatin (P) on day 1 and 120 mg/m2 of etoposide (E) on day 4, 6, 8, every 21 days. Limited disease (LD) patients, achieving complete response (CR) or partial response (PR) after the three initial courses, received radiotherapy (RT) to the pretreatment primary tumor volume and, those achieving CR, additional RT to the brain. During RT, chemotherapy was administered with 50% dose reduction. Forty-three patients were evaluable for therapeutic response. In the 19 patients with LD, CR was achieved in 63% of patients and the PR rate was 32%. In 24 patients with extensive disease (ED), CR was 34% and PR rate was 54%. Median duration of survival was 66 weeks for LD and 48 weeks for ED. Six patients were disease-free after 2 years. Leucocyte count less than 2000/mm3 was seen in 26% of patients; platelet count less than 50000/mm3 was observed in 9%. Nonhematologic toxicity included universal nausea or vomiting and severe neurotoxicity in 7%. These data indicate that PE combination is a very active front-line regimen in SCLC and could be suggested as one of the reference treatments.     

A phase II trial of cyclophosphamide, etoposide, and cisplatin with combined chest and brain radiotherapy in limited small-cell lung cancer: a Cancer and Leukemia Group B Study

Limited-extent small-cell lung carcinoma (SCLC) remains a therapeutic problem with little improvement in complete response (CR) rates and long-term survival in the past 5 years. From June 1984 through January 1985, 56 patients with limited-extent SCLC were enrolled in a Cancer and Leukemia Group B (CALGB) phase II study using five cycles of cyclophosphamide (500 mg/m2 intravenously [IV] day 1), etoposide (80 mg/m2 IV days 1 to 3), and cisplatin (33 mg/m2 IV days 1 to 3) administered at 3-week intervals (CEP), with radiation therapy (50 Gy to chest and 30 Gy to brain) administered concomitant with cycles 4 and 5, followed by three cycles of cyclophosphamide (500 mg/m2 IV day 1), etoposide (80 mg/m2 IV days 1 to 3), and doxorubicin (50 mg/m2 IV day 1). Of 49 patients evaluable for response, the overall response rate was 88%, with 57% CRs. The median overall survival was 14 months; the median duration of CR was 10 months, and nine CRs remain disease free at a median follow-up of 23 months. Toxicity was significant: 56% patients experienced WBC less than 1,000 microL, 32% platelets less than 25,000 microL and 10% hemoglobin less than 7 g/dL. There was one treatment-related septic death. These results are as good as the best previous CALGB study of SCLC, despite a reduction in duration of treatment from 18 to 5 months. We are currently using a variant of this multimodality treatment approach as our standard management for patients with limited-extent SCLC.     

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report

Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC).Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning.Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC.Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC.Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR >2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.     

High-dose induction chemotherapy with cyclophosphamide, etoposide, and cisplatin for extensive-stage small-cell lung cancer

To exploit possible dose-response and combination drug synergism, 20 previously untreated patients with extensive-stage small-cell lung cancer (SCLC) received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg), etoposide (1,200 mg/m2), and cisplatin (120 mg/m2) (HDCEP). HDCEP was followed by four cycles of standard-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV). Response was determined after HDCEP and following CAV. Reevaluation included repeat bronchoscopy and chest computerized tomography (CT), as well as repetition of all initially abnormal studies. All patients were evaluable for response and toxicity. Overall response to HDCEP was 90%, with a complete response (CR) rate of 65% (95% confidence limits, 44% to 86%) and a partial response (PR) rate of 25% (95% confidence limits, 6% to 44%). All patients either maintained or improved their initial response while receiving CAV. Median duration of response was 6 months (range, 2 to 12 months) and median survival was 9.5 + months (range, 2 to 21 + months). All 37 courses of HDCEP were associated with leukopenia (less than 1,000/microL), 92% with thrombocytopenia (less than 20,000/microL), and 84% with fever of greater than 38.5 degrees C. Additional toxicities included bacteremia (24%), nausea and emesis (59%), mucositis (57%), diarrhea (38%), and hemorrhagic cystitis (5%). There were two treatment-related deaths due to infection. A third patient died 4 months after completing HDCEP with pulmonary fibrosis. Although response duration and median survival were not improved, HDCEP produced a high CR rate in ambulatory patients with extensive-stage SCLC.     

Treatment of diffuse histiocytic lymphoma (DHL) with COMLA (cyclophosphamide, oncovin, methotrexate, leucovorin, cytosine arabinoside): a 10-year experience in a single institution

Between March 1974 and December 1983, 83 patients with diffuse histiocytic lymphoma (DHL) were treated with COMLA (cyclophosphamide 1.5 g/m2 day 1; Oncovin (Lilly, Indianapolis) 1.4 mg/m2 days 1, 8, and 15; and cytosine arabinoside 300 mg/m2 and methotrexate 120 mg/m2 days 22, 29, 36, 43, 50, 57, 64, and 71; and leucovorin 25 mg/m2 every six hours X 4, beginning 24 hours after methotrexate). For the purpose of analysis, patients were divided into two groups. Group 1 (n = 54) included patients age 65 or under who had received no prior curative radiotherapy or chemotherapy. Group 2 (n = 29) included all patients over age 65 and patients who had received prior curative radiation therapy or prior minimal chemotherapy. The median time of follow-up for all patients was 28 months. Group 1 included 11 stage II, ten stage III, and 33 stage IV patients. Of 48 evaluable patients in this group, 21 (44%) achieved a complete remission (CR), eight (17%) achieved a partial remission (PR), and 19 (40%) showed no response (NR). Median survival of CR patients was 114+ months, PR patients, 42 months, and NR patients, 13 months. Six CR patients relapsed. The median disease-free survival of CR patients was 108+ months. Group 2 included nine stage II, seven stage III, and 13 stage IV patients. Of 24 patients evaluable for response, eight (33%) achieved a CR, six (25%) achieved a PR, and ten (42%) showed no response. The median survival of CR patients was 114+ months, that of PR patients was 17 months, and that of NR patients, 9 months. Two CR patients relapsed. The median disease-free survival of CR patients had not been reached at 102 months. The regimen was well tolerated in most patients and toxicity was acceptable. We conclude that COMLA is a well tolerated outpatient chemotherapy regimen capable of inducing durable CRs in some patients with DHL. Results achieved with COMLA, however, are inferior to those of more aggressive treatment programs; thus, the use of COMLA as first-line therapy in DHL should be limited to those patients unable to tolerate a more aggressive treatment program.     

Combination chemotherapy with cisplatin and etoposide associated with radiotherapy in the treatment of small-cell lung cancer

Summary A total of 52 consecutive, previously untreated patients with small-cell lung cancer (SCLC) were scheduled to receive six cycles of a combination of etoposide (75 mg/m² per day) and cisplatin (20 mg/m² per day), each cycle given over 5 consecutive days. In all, 28 patients had extensive disease (ED) and 24, limited disease (LD). After three cycles of chemotherapy, all responding patients were given chest radiotherapy (RT) (45 Gy in two split courses and 30 Gy in LD and ED, respectively); only patients with LD who achieved complete remission (CR) after three cycles of chemotherapy were given prophylactic brain irradiation (30 Gy). In the 51 evaluable patients, the overall response rate was 90%, with a 31% CR and a 59% partial remission (PR) rate. In LD and ED patients, 57% and 11% CR rates and 30% and 82% PR rates were noted, respectively. Myelosuppression was the most frequently observed toxicity. The median duration of response was 12 months in LD (range, 3–41+months) and 7 months (range, 2–12 months) in ED; the median survival was 15 months in LD and 9.3 months in ED, respectively. In all 30% of LD patients are alive and well at a minimal follow-up of 18 months. This trial confirms the activity of the cisplatinetoposide combination in SCLC.Bursar, Italian Association for Cancer Research (AIRC)     

Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.     

拓扑替康治疗小细胞肺癌和复发性卵巢癌的临床研究

目的：评价国产拓扑替康（TPT）单药治疗小细胞肺癌及复发卵巢癌的临床疗效和不良反应。方法：患者141例,TPT1．2mg.(m^2)^-1.d^-1,静脉滴注30min,1次／d连用5d,21d周期。可评价疗效者118例,其中小细胞肺癌89例,复发卵巢癌29例,141例患者和286个周期可评价毒副作用。结果：在可评价疗效的118例中,完全缓解（CR）5例,部分缓解（PR）35例,有效率（RR）33．8％,其中小细胞肺癌CR3例,PR26例,RR32．6％,初治与复治的RR分别为50．0％和15．6％;复发卵巢癌CR2例,PR9例,RR37．9％,在可评价毒副作用的141例和286个周期中, 毒副作用是骨髓抑制,Ⅲ、Ⅳ度的中性粒细胞减少61例（43．2％）和81个周期（28．3％）。Ⅲ、Ⅳ度血小板减少18例（12．75）和21个周期（7．3％）。非血液学毒性一般较轻,可耐受。结论IPT是治疗小细胞肺癌和复发卵巢癌有效的药物,对一些常 化疗方案失败的病例仍有效,主要的剂量限制性毒性是骨髓抑制。国产TPT治疗小细胞肺癌和锡期卵巢的疗效和毒性。与国外同类产品相似。     

Cisplatin etoposide versus cisplatin/etoposide/ifosfamide combination chemotherapy in small-cell lung cancer: a multicenter randomized controlled study. Hokkaido Study Group of Treatment for Small-Cell Lung Cancer]

Ninety-two patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, day 1, 3, 5) (PE) or cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2 1, 3, 5)/ifosfamide (2 g/m2, day 1, 2, 3) (PEI) combination chemotherapy. After 2 courses of chemotherapy, patients with limited disease (LD) received chest irradiation with 40-50 Gr. Of the 89 patients evaluable, the overall response rate was 77.8% in PE therapy, and 73.7% in PEI therapy (NS). The complete response rate (CR) of PE v PEI was 13.9% v 21.2% for all patients (NS), 22.2% v 30.4% for LD. Median survival times of PE v PEI for all patients were 55 weeks v 56 weeks (NS). The 2-year survival rate of PE v PEI was 15.4% v 16.5% for all patients (NS). There was no difference of the duration of response in cases with CR or PR between PE and PEI therapy. Leucopenia occurred more often after PEI than after PE therapy (p less than 0.01). These results suggest that PEI is not superior to PE chemotherapy in SCLC.     

Alternating chemotherapy with etoposide plus cisplatin and topotecan plus paclitaxel in patients with untreated,extensive-stage small cell lung carcinoma: a phase II trial of the North Central Cancer Treatment Group

BACKGROUND: The objective of this study was to test the response rate and toxicity of alternating chemotherapy in previously untreated patients with extensive-stage small cell lung carcinoma (SCLC). METHODS: Patients with histologically proven, extensive-stage SCLC, with a performance status of 0-2, and who had received no prior chemotherapy were eligible. The design was a two-stage, Phase II, multicenter trial. Treatment consisted of alternating chemotherapy every 3 weeks with etoposide (100 mg/m(2) on Days 1-3) and cisplatin (30 mg/m(2) on Days 1-3) on Cycles 1, 3, 5 and with topotecan (1 mg/m(2) on Days 1-5) and paclitaxel (200 mg/m(2) on Day 5) on Cycles 2, 4, and 6. Filgrastim support was given with Cycles 2, 4, 6. RESULTS: Forty-four patients were eligible and evaluable. The primary toxicity was myelosuppression. The median absolute neutrophil count was 300/microL with 70% Grade 4 neutropenia. The median platelet count was 58,000/microL with 23% Grade 4 thrombocytopenia. Grade 4 nonhematologic toxicities occurred in 16% of patients. Overall toxicities were not different between the two regimens. There were no treatment-related deaths. Complete or partial responses occurred in 34 patients (77%). The median time to progression was 6.9 months, with a median survival of 10.5 months and with 1-year and 2-year survival rates of 37% and 12%, respectively. CONCLUSIONS: The regimen of alternating chemotherapy was associated with substantial myelosuppression and resulted in a high response rate and good overall survival. The results were similar to those reported in prior trials and did not suggest any improvement in therapy for patients with SCLC.     

拓扑替康单药治疗小细胞肺癌临床研究

目的探讨拓扑替康单药治疗小细胞肺癌(SCLC)的疗效及安全性.方法初治和复治(SCLC)40例,可评价疗效35例,可评价不良反应40例.拓扑替康1.2mg·m     

Intensive alternating combination chemotherapy and high dose chest radiotherapy in small cell lung cancer.

Sixty-nine patients, 32 with limited and 37 with extensive small cell lung cancer (SCLC), were admitted to the present study. Patients with limited disease underwent alternating combination chemotherapy consisting of CAV (cyclophosphamide, adriamycin, vincristine) and PE (cisplatin and etoposide) regimens and concurrent high dose thoracic radiotherapy (6,000 cGy); prophylactic brain irradiation (3,000 cGy) was administered to complete responders. Patients with extensive disease received the same alternating chemotherapy but not radiotherapy. In the 25 evaluable patients with limited disease we obtained an objective response (OR) in 80% with a complete response (CR) in 54% and partial response (PR) in 24%, stable disease (SD) in 4% and progressive disease (PD) in 16%. Median duration of response was 9.5 months for CR and 8.5 months for PR. Median survival was 14 months for all patients with 12% long-term survivors. Toxicity was acceptable. In the 32 evaluable patients with extensive disease we observed 65.6% OR with 18.7% CR and 46.8% PR, 9.3% minimal response and 25% PD. Median duration of response was 7 months for CR and 8 months for PR. Median survival was 10 months for all patients. The treatment was well tolerated. Our study did not show a therapeutic advantage for alternating combination chemotherapy in SCLC and failed to show the use of high dose chest radiotherapy in combined modality for limited disease.     

Alternating chemotherapy with cyclophosphamide, doxorubicin, vincristine and cisplatin, etoposide followed by prophylactic cranial and thoracic irradiation for small cell lung cancer (SCLC): long-term results.

Both CAV (Cyclophosphamide, Doxorubicin, Vincristine) and PE (Cisplatin, Etoposide) are effective and non cross-resistant regimens in the treatment of SCLC. We designed a chemotherapeutic scheme including CAV and PE given in an alternating fashion with the following schedule: Cyclophosphamide 1000 mg/sm, Doxorubicin 50 mg/sm, Vincristine 2 mg/sm I.V. on day 1, alternated every 21 days with Cisplatin 20 mg/sm and Etoposide 80 mg/sm I.V. days 1-5 for 6 cycles. Following chemotherapy (CT) chest radiotherapy in patients (pts) with limited disease (LD) in complete response (CR) or partial response (PR) and prophylactic cranial irradiation (PCI) in CRs were given, 32 pts entered the study and 27 were evaluable: 9/27 (33.3%) had CR (8/15 with LD had CR) and 15/27 (55.5%) PR. The overall median survival was 53.71 weeks: 79.85 weeks for LD pts and 32.86 for ED.4 pts with LD were alive after 2 years and 2 of them are still alive without disease at 44 and 46 months. Toxicity was acceptable in all patients. Alternating chemotherapy with CAV and PE followed by chest and brain RT in responding LD pts is an effective induction treatment for SCLC although long-term survival still remains disappointing.     

A phase II study of the combination of carboplatin and ifosfamide in previously untreated metastatic small cell lung carcinoma.

This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.     

A prospective evaluation of 5-fluorouracil plus cisplatin in advanced squamous-cell cancer of the head and neck

Recent studies have shown improved efficacy of chemotherapy in patients with advanced squamous-cell cancer of the head and neck. Our purpose was to evaluate prospectively the activity of cisplatin plus 5-fluorouracil (5FU) in 37 patients with advanced stage IV squamous-cell cancer of the head and neck. There were two groups. Group 1 consisted of 19 previously untreated patients with either T4 or N3 disease. They received 100 mg/m2 cisplatin (days 1 and 28) and 120-hour infusion of 1,000 mg/m2/24 hours 5FU (days 1 to 5 and 28 to 32). They subsequently were offered preoperative radiotherapy (RT) and surgery. Group 2 consisted of 18 previously treated patients. They received 5FU and cisplatin in the same dosage every 28 days for either recurrent or metastatic disease. It was found that in group 1 there was an 84% response rate (five complete responses (CR) and 11 partial responses (PR) ). Three of those with PR achieved a CR after RT. Seven patients have had RT plus surgery and are disease free at 8 to 27 month follow-up. Six patients (one CR, five PR) refused surgery and progressed within 4 months. In group 2 there was an 11% response rate after two cycles (two PR), three patients had a minimal response (MR, less than 50% response) and received a mean of four cycles of treatment. Three patients with stable disease received a mean of four cycles of chemotherapy until progression. Two of 11 patients who had received previous chemotherapy plus RT showed an MR; nine of these patients had shown a response to their previous chemotherapy. Only one of 14 patients who had RT plus chemotherapy had a PR, and three had MR. Of five patients who had previous surgery, only one had a PR. All five had received chemotherapy as well. It was concluded that 5FU plus cisplatin is an effective combination in previously untreated patients. In previously treated patients with recurrent disease, there is a substantially lower response rate.     

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer

Background: We conducted a phase I/II trial to assess the feasibilityand activity of VIP-E chemotherapy in small-cell lung cancer. End-points weretreatment-related morbidity and mortality, response to treatment, duration ofresponse, and survival.Patients and methods: Two cycles of combination chemotherapy followedby granulocyte colony-stimulating factor (G-CSF) were given at a dose ofetoposide (500 mg/m²), ifosfamide (4000mg/m²), cisplatin (50 mg/m²), and epirubicin(50 mg/m²) to 100 consecutive patients with SCLC. Thirtypatients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dosechemotherapy with autologous peripheral blood stem cell transplantation(PBSCT) at a cumulative dose of etoposide 1500 mg/m²,ifosfamide 12,000 mg/m², carboplatin 750 mg/m²and epirubicin 150 mg/m² (VIC-E). Surgical resection ofprimary tumor was attempted at the earliest feasible point. Thoracicirradiation was given after completion of chemotherapy.Results of conventional-dose VIP-E: 97 patients were evaluable forresponse. Objective response rate was 81% in LD-SCLC (33% CR,48% PR; excluding patients in surgical CR) and 77% in ED-SCLC(18% CR, 58% PR). Treatment mortality was 2%. Mediansurvival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survivalwas 36% in LD and 0% in ED SCLC.Results of high-dose VIC-E: All 30 patients improved on or maintainedprior responses. Four patients (13%) died of treatment-relatedcomplications. Median survival was 26 months in LD-SCLC and 8 months inED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC.Conclusion: VIP-E chemotherapy is an effective induction therapy forSCLC. Compared with traditional protocols such as ACO orcarboplatin/etoposide, response rates are slightly improved, while survivalis not different. In the LD SCLC subgroup, high-dose chemotherapy improvedresponse rates and survival, especially for patients in surgical CR prior tohigh-dose therapy. In ED SCLC, however, higher response-rates did nottranslate into improved survival. Selected LD-SCLC patients with good partialor complete remissions after prior therapy may benefit from HDC and PBSCT.     

拓朴替康治疗小细胞肺癌的临床观察

目的:探讨以拓朴替康联合顺铂方案治疗小细胞肺癌(SCLC)的疗效及安全性.方法:观察组60例,化疗方案为TP(拓朴替康 顺铂).拓朴替康1.20mg/m2/d,静滴30min,每日1次,连用5日;DDP 80mg/m2iv gtt,分3天使用.对照组60例,化疗方案为PE(VP-16 顺铂).VP-16 100mg/m2 iv gtt,d1,3,5;DDP 80mg/m2iv gtt,分3天使用.21天为1周期,2个周期评价疗效,1个周期评价不良反应.结果:观察组CR 8例,PR 30例,有效率63.3%,主要不良反应为血液学毒性,非血液学毒性较轻微,一般均可耐受.对照组CR 6例,PR 34例,有效率66.7%.两组间疗效及不良反应均无显著性差异(P＞0.05).结论:拓朴替康联合顺铂化疗方案治疗SCLC有效,局限期疗效优于广泛期.     

拓朴替康治疗小细胞肺癌近期疗效观察

目的 观察枯扑替康治疗小细胞肺癌的疗效和毒副反应。方法 拓扑替康单药治疗剂量为1．2mg/m^2,联合剂量为1mg/m^2,静脉输注30分钟,连用5天,联合卡铂剂量为350mg/m^2,21天为一周期,连用2个周期评价疗效。结果 17例中CR1例,PR12例,有效率76．5％。初治的有效率为90％,复治的有效率为57．1％。3例脑转移的患者、2例PR。毒副反应主要为中性粒细胞及血小板减少,18例中17例有不同程度的中性粒细胞减少,其中达Ⅲ、Ⅳ度的13例,血小板达Ⅲ、Ⅳ度8例。结论 拓朴替康单药治疗复发小细胞肺癌疗效确切,联合卡铂治疗可以耐受,疗效增加。主要的毒副反应是中性粒细胞和血小板减少。     

Sequential administration of cisplatin-etoposide followed by topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II study

PURPOSE: To evaluate the activity of the sequential administration of cisplatin-etoposide (PE) followed by topotecan (TOP) in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated patients with extensive stage SCLC received 4 cycles of cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 every 21 days followed by 4 cycles of TOP 1.5 mg/m(2) IV on days 1-5 every 21 days. RESULTS: Thirty-eight patients were entered in the study. Their median age was 63 years and the performance status (WHO) was 0 for 5, 1 for 25 and 2 for 8 patients. All patients were evaluable for toxicity and 32 for response to PE and 25 to TOP. Of the 38 patients receiving PE, 1 (3%) patient achieved complete response (CR) and 17 (45%) partial responses (PR) for an overall response rate to PE of 47% (95% confidence interval: 36.7-68.5%). Four (23.5%) of the 17 patients with PR after PE, achieved CR with TOP. None of the patients with stable or progressive disease after PE responded to TOP. The response rate of the 27 patients receiving TOP following PE was 15% (95% confidence interval: 1.4-28.2%). After a median follow up of 9 months, the median duration of response was 6.5 months, the time to tumor progression 6.5 months, the median survival 8.5 months and the 1-year survival 34%. A total of 136 cycles of PE and 89 cycles of TOP have been administered with a median of 4 cycles/patient for each regimen. There were 2 toxic deaths after PE associated with grade IV febrile neutropenia. Treatment delays due to toxicity occurred in 17 (12%) cycles of PE and 20 (22%) cycles of TOP while doses were reduced in 7 (5%) and 4 (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia occurred in 24, 2 and 3% of PE cycles and 21, 12 and 1% of TOP. Non-hematologic toxicity was mild. The delivered dose intensity was 100% for PE and 93% for TOP. CONCLUSIONS: The sequential administration of TOP after PE is associated with manageable toxicity and may increase the number of CRs in patients with chemosensitive extensive stage SCLC. However, based on this data and the lack of survival benefit in a previous phase III study, the sequential regimen should not be used outside of a clinical trial.