Phase II study of cisplatin, maytansine, and chlorozotocin in small cell lung carcinoma (EST 2578)

Seventy-three patients with small cell lung carcinoma refractory to standard chemotherapy were entered in this phase II randomized study of cisplatin, maytansine, and chlorozotocin. Of the 58 evaluable patients, only one partial response was observed among 21 patients given cisplatin, and no responses were seen among 19 given maytansine or 18 given chlorozotocin. One patient treated with chlorozotocin and two treated with cisplatin experienced life-threatening thrombocytopenia. One third of the maytansine-treated patients experienced moderate or severe neurologic toxicity. The overall median survival was 9.7 weeks. Chlorozotocin treatment was associated with inferior survival (7.7 weeks).     

Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer

Carboplatin, a cisplatin analog without significant clinical nephrotoxicity, has been evaluated in the treatment of 56 patients with small cell lung carcinoma at a dose of 300-400 mg/m2 iv monthly in a phase II study. Twenty-three patients (41%) achieved a response, including five (9%) complete remissions. Of 30 previously untreated patients, 18 (60%) achieved a response, including three (10%) complete remissions. Median response duration was 4.5 months (range, 2-9). No nephrotoxicity was seen and hydration was not required. Nausea or vomiting occurred in only 24 patients (43%) and was rarely severe. Myelosuppression was dose-limiting: 20 patients (36%) developed leukopenia and eight (14%) developed thrombocytopenia, but leukopenic infections occurred in only three patients. Carboplatin is a very active new agent in the treatment of small cell lung cancer, with less toxicity and better tolerance than cisplatin. It merits further investigation in combination chemotherapy and against non-small cell lung cancer.     

Cisplatin and etoposide combination chemotherapy for refractory small cell carcinoma of the lung

Twenty-nine patients with refractory recurrent small cell carcinoma of the lung were treated with cisplatin (40 mg/m2) and etoposide (200 mg/m2) each day for 3 days, repeated every 3-4 weeks. Fifteen of these patients had received etoposide in their original treatment regimen. Fifteen (52%) of all patients had a major response, as did nine (60%) of the patients with prior exposure to etoposide. Myelotoxicity was moderately severe. The median duration of responses was 3 months (range, 6-36 weeks). This study suggests synergism between cisplatin and etoposide. The toxicity seen in this heavily pretreated group of patients suggests that smaller doses be studied in this group. The synergism may be best utilized in the initial regimens against small cell lung cancer.     

High-dose cisplatin with fluid and mannitol-induced diuresis in advanced lung cancer: a phase II clinical trial of the EORTC Lung Cancer Working Party (Belgium)

A phase II clinical trial of high-dose cisplatin (120 mg/m2 iv every 3 weeks), with fluid and mannitol-induced diuresis, was conducted in 81 patients with advanced lung cancer. Partial remissions were documented in 26% of 75 evaluable cases for a median duration of 3.5 months. Adenocarcinoma and small cell anaplastic carcinoma were more responsive than epidermoid carcinoma, with partial response rates of 35%, 30%, and 18%, respectively. The median survival of responders (8.5 months) was significantly longer than the survival of nonresponders (4 months) (P less than 0.02). Myelosuppression was mild. Renal toxicity with peak serum creatinine greater than 2.5 mg/100 ml occurred in eight patients, with one death occurring due to toxicity. Cisplatin is an active drug in advanced lung cancer.     

Phase II study of vindesine, cisplatin, and hexamethylmelamine (VCH) in small cell carcinoma of the lung

Forty-two patients with small cell carcinoma of the lung were treated with cycles given every 28 days consisting of a combination of vindesine (3 mg/m2 if on Days 1 and 15), cisplatin (75 mg/m2 iv on Day 1), and hexamethylmelamine (200 mg/m2 orally on Days 8-22). Thirty-four patients were evaluable for response. Partial remission (PR) or complete remission (CR) was noted in seven (three CRs and four PRs) of nine previously untreated patients (77%) and in eight (one CR and seven PRs) of 25 patients treated previously with intensive chemotherapy (32%). This drug combination deserves consideration for inclusion in sequential combination chemotherapy regimens.     

Lack of efficacy of vinblastine and cisplatin in patients with progressive small cell carcinoma of the lung

Twenty patients with small cell carcinoma of the lung resistant to primary therapy, or relapsing after an objective response to initial treatment, were treated with vinblastine plus high-dose cisplatin chemotherapy. One patient achieved a partial remission lasting 4 months, while 19 patients had no objective response to this regimen. The median survival from the time of disease progression to death was 2.5 months (range, 1-7), with an overall median survival of 13 months (range, 5-31; diagnosis to death). In our patients, vinblastine plus cisplatin given as salvage therapy did not produce a significant response rate or survival prolongation.     

Chemotherapy of cerebral metastasis of lung cancer

Between November 1983 and November 1988, 60 patients with cerebral metastases arising from primary lung cancer were treated with chemotherapy. Thirty patients received a 5-day course of cisplatin (total dose: 200 mg/sq.m). The remaining 30 patients received VP 16 in doses of 250 mg/sq.m. administered 12-hourly by intravenous infusion over one hour (total dose: 1,500 mg/sq.m.). Twenty-seven percent of the patients who received cisplatin showed objective responses as assessed by computerized tomography; 10% had serious toxic reactions. Thirty percent of the patients who received VP 16 showed objective responses, but 43% had severe bone marrow aplasia resulting in a 33% death rate due to infection. The median survival of responders was 8 months in both treatment groups. The objective response rates as assessed by histology were 33% in patients with oat-cell carcinoma and 27% in patients with other histological types. VP 16 must be abandoned, being too toxic in high doses. High-dose cisplatin can be used in the treatment of cerebral metastases of lung cancer, side by side with radiotherapy.     

Gemcitabine方案复治晚期非小细胞肺癌

目的：探讨Gemcitabine(健择）与顺铂联合化疗方案复治常规方案无效晚期非小细胞肺癌的临床疗效及其不良反应。方法：健择与顺铂联合方案复治22例晚期晨小细胞肺癌二周期，健择每周期第1、8、15天静脉滴注1000mg/m^2，顺铂每周期第1天静脉滴注100mg/m^2，结果：可评价疗效22例，8例获得部分缓解（PR），总有效率36％，全组均可评价不良反应，约30％分别发生Ⅲ-Ⅳ度的血红蛋白下降，白细胞下降，血小板下降和恶心／呕吐，其他毒副反应均轻度可耐受，结论：健择与顺铂联合方案复治常规方案无效晚期非小细胞肺癌有一定的疗效，毒副作用可耐受，是复治晚期非小细胞肺癌较理想的治疗方案之一。     

Phase II trial evaluating continuous infusion of etoposide, cisplatin, and hexamethylmelamine in extensive-disease small cell carcinoma of the lung

A total of 27 untreated and 24 previously treated patients with extensive-disease small cell lung cancer (SCLC) were treated with a combination chemotherapeutic regimen of continuous-infusion etoposide for 5 days, cisplatin, and hexamethylmelamine. of 25 evaluable patients with untreated SCLC, three (12%) achieved a complete response and 16 (64%) achieved a partial response. Among 23 evaluable patients with relapsed SCLC there were no complete responses and nine (39%) achieved a partial response. Median survival times were 252 and 109 days for the above groups, respectively. Myelotoxicity, especially thrombocytopenia, was moderately severe. Other toxic effects, including renal and neurologic, were minimal. These results compare favorably with other regimens including etoposide and cisplatin. Our results further confirm the activity of etoposide and cisplatin as both initial therapy and as a salvage regimen in the management of patients with extensive-stage SCLC.     

Treatment of recurrent small cell lung carcinoma with vindesine and cisplatin

Thirty-two males with recurrent small cell lung cancer after previous remission were treated with vindesine (3-4 mg/m2) plus cisplatin (60-100 mg/m2). Six patients (19%) responded to this therapy with two complete (CR) and four partial remissions. Minor responses were seen in another ten patients (32%). In patients with CR survival from start of treatment lasted 61 and 38 weeks; in patients who did not achieve CR median survival was 12 weeks. Nausea and vomiting were the predominant side effects, while only mild to moderate myelosuppression was noted. The vindesine and cisplatin regimen demonstrated significant activity against heavily pretreated small cell lung cancer, although chemotherapeutic response was poor in regions of prior irradiation.     

Lymphoepithelioma-like carcinoma of the lung: experience with ten cases.

OBJECTIVE: Lymphoepithelioma-like carcinoma of the lung (LELC) is a rare form of non-small cell lung cancer predominantly affecting young non-smoking Asians, and there has been only limited experience in its palliative chemotherapy and radiotherapy. We investigated tumour response, time to progression and survival of LELC patients who received such treatment. DESIGN: We prospectively recruited patients with confirmed advanced LELC who were treated with chemoradiotherapy in our unit, a regional tertiary referral centre for lung cancer treatment. RESULTS: There were 10 patients (five males, age 47 +/- 9.8 years, median follow-up 22 months) with advanced LELC (respectively 1, 4, and 5 patients at TNM stage IIIA, IIIB and IV) who received systemic chemotherapy and radiotherapy. The primary chemotherapy regimen consisted of 5-fluorouracil/leucovorin/cisplatin. The response rates to 5-fluorouracil/leucovorin/cisplatin were 60% partial response, 10% stable disease, and 30% progressive disease. Eight patients were also given local radiotherapy. Five patients received salvage chemotherapy when disease progressed after primary chemotherapy. The overall median survival was 23.4 +/- 4.7 months. CONCLUSION: The encouraging response to combination chemotherapy with 5-fluorouracil/leucovorin/ cisplatin, although empirical, supports its use with radiotherapy in unresectable lymphoepithelioma-like carcinoma of the lung.     

Use of cisplatin, cyclophosphamide, vincristine, and doxorubicin for the treatment of non-small cell lung cancer

Forty-four evaluable patients with non-small cell carcinoma of the lung were treated with cisplatin, cyclophosphamide, vincristine, and doxorubicin. The overall response rate was 57%. The 16% who had complete response had a median survival of 81 weeks.     

Doxorubicin,cisplatin, and fluorouracil combination therapy for metastatic esophageal squamous cell carcinoma

The chemotherapy regimen currently used for treating esophageal and gastric carcinoma has been either epirubicin, cisplatin, and fluorouracil (5‐FU) or docetaxel, cisplatin, and 5‐FU. Here, we report the efficacy and toxicity of doxorubicin, cisplatin, and 5‐FU for only esophageal squamous cell carcinoma (ESCC). Between January 2000 and October 2008, a total of 41 ESCC patients with a distant metastasis were enrolled. The most common sites of metastasis were liver (26, 63.4%), lung (9, 22.0%), and bone (8, 19.5%). Doxorubicin was administered on day 1 at 30 mg/m², cisplatin on days 1–5 at 14 mg/m²/day, and 5‐FU on days 1–5 at 700 mg/m²/day. The median number of cycles was 2.0 (range 1‐8). The dose intensities of doxorubicin, cisplatin, and 5‐FU were 92.9, 92.4, and 92.5%, respectively. The overall response rate was 43.9%; one showed complete response, 17 showed partial response, 13 showed a stable disease, and 10 showed progressive disease (PD). The median survival time was 306 days (95% CI = 74–935) and the 1‐year survival rate was 37.6%. Grade 3 neutropenia was seen in seven patients and grade 4 in one patient. Grade 3 fatigue, anorexia, mucositis, and diarrhea were observed in three, two, two, and one patient, respectively. This regimen is effective as a first‐line therapy for ESCC with distant metastasis.     

Low-dose cisplatin plus oral tegafur and uracil for the treatment of lung metastases of hepatocellular carcinoma

BACKGROUND/AIMS: An effective treatment for unresectable multiple lung metastases of hepatocellular carcinoma have never been established. METHODOLOGY: Six patients received the chemotherapy described herein as an initial treatment for lung metastases of hepatocellular carcinoma. Low-dose cisplatin infusion plus oral tegafur and uracil administration combination therapy essentially consisted of cisplatin (10 mg/day over 1 hour) infused on days 1-5 every week and oral tegafur and uracil (300 mg/day) administrated every day. This treatment was repeated weekly for essentially 4 consecutive weeks. RESULTS: Complete response was observed in no cases and partial response in 3 cases, while no change was observed in 4 cases and progressive disease in one case. An overall response rate was 50%. The serum alpha-fetoprotein and des-Y-carboxyprothrombin were reduced in most of the patients. Leukopenia of grade 2 was observed in only 1 (17%) patient. Thrombocytopenia of grade 2 was observed in 2 (33%) patients. Nausea (up to Grade 2) was occurring in 4 (67%) patients. Three patients with no other distant metastasis survive more than two years after lung metastasis, and the quality of life of these patients are well preserved. CONCLUSIONS: Low-dose cisplatin infusion combined with oral tegafur and uracil administration for the treatment of lung metastases of hepatocellular carcinoma may be an effective regimen with a high response rate and acceptable toxicities, although a larger study will be necessary to confirm the efficacy.     

A Phase II Trial of Irinotecan and Cisplatin in Patients with Metastatic Neuroendocrine Tumors

The role of systemic chemotherapy in the treatment of patients with metastatic neuroendocrine tumors is controversial. While combination regimens containing cisplatin and etoposide have activity against more aggressive neuroendocrine tumor variants, such regimens appear to have little efficacy in patients with well-differentiated neuroendocrine tumor subtypes. The combination of irinotecan and cisplatin is active both against small cell lung cancer and in upper gastrointestinal malignancies but has not been prospectively evaluated in patients with metastatic neuroendocrine tumors. We therefore assessed the efficacy of an irinotecan/cisplatin combination in patients with this disease. Eighteen patients with metastatic neuroendocrine tumors (excluding small cell carcinoma) were treated with irinotecan, 65 mg/m², and cisplatin, 30 mg/m², administered weekly for 2 of every 3 weeks. Patients were followed for evidence of toxicity, response, and survival. The toxicities associated with this regimen were mild and included myelosuppression, nausea, and diarrhea. Only one radiologic response was observed among four patients with poorly differentiated neuroendocrine tumors. No radiologic responses were observed in 14 patients with well-differentiated tumors. The median overall survival duration of patients treated with this regimen was 11.4 months. We conclude that while the combination of irinotecan and cisplatin may have activity in aggressive neuroendocrine tumor subtypes, this combination is inactive in patients with well-differentiated neuroendocrine tumors. This work received financial support from Pfizer Corporation, M. H. Kulke is supported in part by NIH grants K23 CA 093401 and K30 HL04095 and gifts from Dr. Raymond and Beverly Sackler, the Stephen and Caroline Kaufer fund for neuroendocrine tumor research, and the Caring for Carcinoid Foundation.     

紫杉醇联合不同铂类治疗晚期肺鳞癌的临床研究

目的评估紫杉醇分别联合顺铂、卡铂、奈达铂对晚期肺鳞癌的近期疗效和毒副反应。方法 84例晚期肺鳞癌患者随机分为三组,每组28例,分别接受紫杉醇联合顺铂、紫杉醇联合卡铂、以及紫杉醇联合奈达铂方案化疗,每21天为一周期,两周期后评价疗效和毒副反应。结果紫杉醇联合顺铂、卡铂、奈达铂治疗晚期肺鳞癌有效率分别为57.14%、53.57%、28.57%,紫杉醇联合顺铂或卡铂治疗晚期肺鳞癌的有效率优于紫杉醇联合奈达铂,差异具有统计学意义(P<0.05),紫杉醇联合顺铂与其联合卡铂治疗晚期肺鳞癌的疗效相当,P>0.05。紫杉醇联合顺铂组恶心呕吐发生率最高,紫杉醇联合卡铂组血小板减少最明显,而紫杉醇联合奈达铂组则无明显毒副作用。结论紫杉醇联合顺铂或卡铂可作为治疗晚期肺鳞癌的一线治疗方案,而紫杉醇联合奈达铂因无明显毒副作用可能更适宜晚期肺鳞癌的年老体弱者化疗。     

Combination chemotherapy with vindesine, etoposide, and cisplatin in non-small cell lung cancer: a pilot study of the Southeastern Cancer Study Group

Ninety-two patients with advanced non-small cell lung cancer were treated with a combination chemotherapy regimen containing cisplatin, vindesine, and etoposide. Eighteen patients (20%) achieved major responses to therapy (three complete responders and 15 partial responders). Response rates were similar in each histologic subtype. Initial performance status was an important determinant of response; 42% of the patients with a Karnofsky performance status greater than or equal to 70% responded versus 5% of those with a performance status less than 50%. The median duration of partial response was 21 weeks; complete responders had a median response duration of 50 weeks. The median survival for the entire group was 23.5 weeks. Toxicity with this regimen was acceptable; myelosuppression was the major toxic effect and was severe in only 10% of the patients. This regimen produced response rates comparable to those reported with other combinations containing cisplatin. Survival advantage in patients receiving this treatment is not established.     

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Purpose According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC.Methods We retrospectively reviewed the clinical information of 12 patients with LCNEC.Results Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR.Conclusions The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.     

紫杉醇联合铂类药物治疗晚期非小细胞肺癌的临床研究

目的评价紫杉醇联合铂类药物对晚期非小细胞肺癌的客观疗效及毒副作用。方法经病理组织学证实的晚期非小细胞肺癌59例，采用紫杉醇135mg／m^2，静脉滴注，第1天，顺铂80mg／m^2，分3d给药，第2～4天，或卡铂350mg／m^2。静脉滴注，第2天，21天为1个周期，2个周期以上评价疗效及毒副作用。结果全组PR24例，SD23例，PD12例，总有效率为40.7％。主要毒副作用为恶心，呕吐、骨髓抑制、关节肌肉痛等。大部分为Ⅰ～Ⅱ度不良反应，患者耐受良好。结论紫杉醇联合铂类方案是1种对晚期非小细胞肺癌有效的治疗方案，毒副作用轻，值得临床进一步研究应用。     

Plasma growth hormone (GH)-releasing hormone levels in patients with lung carcinoma

OBJECTIVE: The aim was to investigate the serum levels of growth hormone releasing hormone and GH in patients with lung carcinoma. DESIGN After an overnight fast a plasma sample was collected for determination of growth hormone releasing hormone and GH. PATIENTS: The investigation was performed in 28 patients with non small cell lung carcinoma, in 44 patients with small cell lung carcinoma, and 10 patients with non malignant lung disease. A group of 37 normal subjects served as control. MEASUREMENTS: Growth hormone releasing hormone and GH were determined by radioimmunoassay. RESULTS: Patients with small cell lung carcinoma showed higher plasma growth hormone releasing hormone levels (49 +/- 9.4 ng/l) than control subjects (16.3 +/- 2.1 ng/l; P less than 0.05), patients with non small cell lung carcinoma (23.9 +/- 8.8 ng/l; P less than 0.05), and patients with non malignant lung disease (12.7 +/- 5.5; P less than 0.05). Basal GH level was lower than 5 micrograms/l in all patients except five patients with small cell lung carcinoma and one patient with non small cell lung carcinoma. CONCLUSIONS: The higher plasma growth hormone releasing hormone levels in patients with small cell lung carcinoma compared to normal controls and patients with non small cell lung carcinoma and patients with non malignant lung disease, confirm the frequent neuroendocrine activity of this particular tumour.