Cyclophosphamide, adriamycin and vincristine (CAV) in the treatment of small cell lung cancer

Thirty-nine previously untreated small cell lung cancer patients received cyclophosphamide (CTX) + adriamycin (ADM) + vincristine (VCR) (CAV). The doses initially used were CTX 1,000 mg/body day 1, ADM 50 mg/body day, VCR 1 mg/body day, 8, 15 or 2 mg/body day(group A). Later, CTX 1,000 mg/m2 day, ADM 60 mg/m2 day, VCR 1.4 mg/m2 day were used. All patients had PS 0-3, 24 had limited disease (LD) and 15, extensive disease (ED). The overall response rate and the complete response (CR) rates were 63% (15/24) and 21% (5/24) for LD, and 21% (3/14) and 0% (0/14) for ED, respectively. The median response durations were 22 weeks for LD and 33 weeks for ED. The median CR duration in LD patients was 23 weeks. Twelve LD and 1 ED patient received thoracic radiotherapy (RT) optionally after 2-4 courses of CAV therapy. Eventually, 8 patients achieved CR. The median survival for LD, ED and all cases were 43 weeks, 37 weeks and 41 weeks, respectively. The 1, 2 and 3-year survival rates were 42, 25 and 21% for LD, and 40, 7 and 0% for ED. Three patients were long-term disease-free survivors (greater than 3 years), and these had LD and received RT. There were 3 chemotherapy-related deaths (2 patients with leukopenia + infection, 1 patient with drug-induced pneumonitis). The survival results of CAV therapy in our hospital were comparable with the recent results of chemotherapies available against small cell lung cancer.     

A combination chemotherapy consisting of vincristine, etoposide and cyclophosphamide (VEC) for small cell carcinoma of the lung

Twenty-nine patients with small cell carcinoma of the lung were treated with a combination therapy consisting of vincristine 1 mg/m2 i.v. day 1, etoposide 200 mg/body p.o day 1-5 and cyclophosphamide 500 mg/m2 i.v. day 1 (VEC) in 3 week interval. After 2 courses of VEC, four out of 10 patients with limited disease (LD) showed a complete response (CR), while 7 out of 19 patients with extensive disease (ED) obtained a CR. Six patients with LD and 6 patients with ED received subsequent radiotherapy to primary tumors and to regional lymph nodes, and 5 with LD and 3 with ED attained a CR. Overall complete response was observed in 9 patients (90%) in LD and 10 patients (53%) in ED. The median duration of survival was 17 months in complete responders with LD and that was 12 months in those with ED. Dose limiting toxicity of the VEC regimen was leukopenia which occurred in most patients and thrombocytopenia was less frequent. Non-hematologic toxicities containing alopecia, numbness, nausea and others were acceptable and well tolerated.     

Results of 2 multicenter therapy studies in inoperable non-small cell bronchial cancer

A total of 166 patients with non-small cell lung cancer (NSCLC) were included in two multicenter trials testing different treatment regimens. In study I, 116 patients received 4 cycles of aggressive polychemotherapy consisting of cis-platinum 100 mg/m2 (day 1), etoposide 100 mg/m2 (days 4-6), and vindesine 3 mg/m2 (day 1) (CEV); patients without distant metastases subsequently received chest irradiation with 50 Gy. In study II, 50 patients were treated with monochemotherapy consisting of etoposide 250 mg/m2 (days 1-3), and ifosfamide 5 g/m2 as 24-h infusion (day 29). While this program was repeated in responders with extensive disease (ED), patients with limited disease (LD) subsequently received chest irradiation with 50 Gy using 20 mg/m2 cis-platinum weekly as a radiosensitizer. Response rates (CR + PR) to chemotherapy were higher in study I than in study II, and were 26% (CR 3%) vs. 8% (CR 0%) for all patients, 18% (CR 0%) vs. 4% (CR 0%) for ED, and 45% (CR 11%) vs. 13% (CR 0%) for LD. The increase in response rates by radiotherapy was marginal in study I (CR + PR 47%, CR 18%), but remarkable in study II (CR + PR 42%, CR 29%). While median survival was slightly longer in study I than in study II for ED (7.7 vs. 6.6 months) and LD (14.4 vs. 12.0 months), the 2-year survival rate was in favor of study II (10% vs. 25%). Toxicity was clearly more pronounced in study I, including 3 lethal complications and 16 discontinuations of therapy due to side effects or refusal. Thus, while in ED the efficacy of both treatment regimens was very restricted, in LD radiotherapy with cis-platinum as a radiosensitizer achieved a relatively high 2-year survival rate which justifies further testing of this treatment strategy.     

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.     

Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer.

PURPOSE: The antineoplastic activity of carboplatin and etoposide may be improved by the addition of vincristine (CEV) because of its low myelosuppressive potential and its activity in small-cell lung cancer (SCLC). A phase II study with CEV was carried out. PATIENTS AND METHODS: One hundred twenty-one untreated patients with SCLC (63 with limited disease [LD], 58 with extensive disease [ED]) were treated with a combination of 300 mg/m2 intravenous (IV) on day 1, etoposide 140 mg/m2 IV daily on days 1 to 3, and vincristine 1.4 mg/m2 IV on days 1, 8, and 15 every 4 weeks. RESULTS: A 90% rate overall response rate including 56% complete responses (CRs) was achieved in LD and an 83% overall response rate including 35% CRs was observed in ED. Median survival time was 13 months in limited disease and 9.5 months in extensive disease. The 24 and 36 months survival rates were 29% in LD and 9% in ED. Myelosuppression was the main form of toxicity. CONCLUSION: The combination of CEV is a new active and well-tolerated regimen in the treatment of SCLC. Prospective randomized studies of CEV with conventional chemotherapy are warranted.     

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)     

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.     

Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (Adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy

Seventy-one previously untreated patients with small cell lung cancer (SCLC) received a combination of VP-16, vincristine, doxorubicin (Adriamycin), and cyclophosphamide (EVAC) repeated every three weeks. Limited-disease (LD) patients and extensive-disease (ED) patients achieving a complete response (CR) or partial response (PR) after four to six cycles of EVAC received 4,000 rads over four weeks whole-brain radiotherapy (RT) and 5,000 rads over five weeks RT to the original pulmonary primary and mediastinum. ED patients with persisting disease outside the chest after six cycles of EVAC continued chemotherapy and did not receive RT. After RT was completed, EVAC was continued for a total treatment duration of 24 months. Of 65 patients evaluable for response 76% (25 of 33) of LD patients and 34% (11 of 32) of ED patients achieved a CR prior to RT; two additional ED patients achieved a CR after RT. Median survival for all 71 patients was 48 weeks (range, one to 207 weeks); median survival for 33 LD patients was 92 weeks and for 38 ED patients it was 36 weeks. Nine of 25 LD patients and 10 of 13 ED patients have relapsed from CR. The EVAC-RT protocol is promising in view of the high CR rate and long remission duration achieved, especially among patients with LD.     

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.     

Combination chemotherapy with low doses of weekly Carboplatin and oral Etoposide in poor risk small cell lung cancer

Sixty patients with poor prognostic features, either with extensive disease (ED) or limited disease (LD) small cell lung cancer (SCLC), were treated on an out-patient basis with Carboplatin 80 mg/m2 weekly for 3 weeks and oral Etoposide, at a dose of 100 mg, every other day for 21 days. The treatment was repeated every 5 weeks. Responding patients with LD were also treated with thoracic irradiation and those who achieved complete response (CR) received prophylactic cranial radio-therapy. The overall response rate (RR) was 32.1% with 8.9% CR. The responses were better for LD (RR 58.3%, CR 25%, partial response, PR 33.3%), than those for ED (RR 25%, CR 4.5%, PR 20.5%). The median time to progression (TTP) was 4.8 months and the median survival 5.5 months. These poor results could be attributed to the bad performance status and the presence of visceral and brain metastases in this group of patients. The results could also be due to the lower maximum concentration (Cmax) and higher T1/2 of Etoposide, as measured in the blood and urine probably due to the modified regimen used in our study and to the organ insufficiency in this selected group of patients. Although, toxicity was generally mild and manageable, two toxic deaths occurred. In conclusion, this regimen appears to have a lower efficacy in terms of response and survival than that obtained in other studies using Cisplatin or Carboplatin plus Etoposide in a similar way. Therapy with this regimen, though less toxic, may not be a reliable alternative in elderly patients with visceral metastases and ECOG performance status > or = 2.     

Pilot phase II study of hybrid chemotherapy of CAV-PVP in small cell lung cancer (SCLC)

A pilot phase II study of a hybrid chemotherapy for SCLC has been conducted between October 1986 and March 1988. Dose and schedule of the regimen were as follows: CTX, 700 mg/m2, on day 1; ADM 30 mg/m2, on day 1; VCR, 1.4 mg/m2, on day 1 (CAV); and CDDP, 60 mg/m2, on day 8; VP-16, 100 mg/m2, on days 8 and 9 (PVP). Courses were repeated q. 4 weeks up to 6 cycles. Patients with LD received chest irradiation at a dose of 50 Gy when maximal response was achieved. Thirty-six patients were fully evaluated for tumor response and toxicity. All 18 patients with LD responded to the regimen including 11 CRs (61%); there were 7 CRs (39%) and 9 PRs (50%) in patients with ED. Fourteen of the 18 patients with LD have survived for 7 to 22 months, against 12.8 months in ED patients. The major toxicity was myelosuppression, but it was well tolerated. These results indicate that hybrid chemotherapy is highly effective for SCLC, and warrants further clinical trials.     

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.     

Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer

Thirty-two previously untreated, fit patients with small-cell lung carcinoma (SCLC) were treated with an intensive combination chemotherapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m2 IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m2 IV days 1 to 3, repeating at 28-day intervals for six courses. Limited-disease (LD) patients were given concurrent hyperfractionated radiotherapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% with 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% 2-year survival and for ED patients 9.5 months with a predicted 14% 2-year survival. Hematologic toxicity was severe with 100% developing World Health Organization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of neutropenic infection or thrombocytopenia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than those reported for less toxic conventional regimens.     

TPF方案诱导化疗加同期顺铂化放疗治疗晚期鼻咽癌的临床研究

 目的　探讨多西紫杉醇（TAX）、顺铂（DDP）、5-氟尿嘧啶（5-Fu）三药联合方案诱导化疗加DDP同期放化疗治疗晚期鼻咽癌的近期疗效及可行性。方法　40例初诊局部晚期（UICC分期Ⅲ、Ⅳ期）鼻咽癌患者入组,随机分为诱导化疗加DDP 3周方案组（A组）,诱导化疗加DDP单周方案组（B组）。两组均先行2个疗程诱导化疗,方案为TAX 60 mg／m2第1天;DDP 60 mg／m2第1天;5-Fu 600 mg／m2 第1天至第5天,每3周重复,共2个周期。第7周开始放疗,放疗第1天同时行化疗。A组：DDP 80 mg／m2第1天,每3周1次,共2次;B组： DDP 30 mg／m2第1天,每周1次,共6次。放疗采用二维适形照射,鼻咽原发病灶68～72 Gy,34～36次,7周,颈部淋巴结阳性区60～66 Gy,30～33次,6～6.5周。结果　40例共完成78个疗程诱导化疗,A、B组各1例出组。38例可评价疗效和不良反应。A组17例完成2个疗程同期DDP化疗;B组10例按计划完成6个周同期化疗,4例完成5周化疗,4例完成4周化疗,1例只完成2周化疗。诱导化疗后CR 4例（10.5 %）,PR 27例（71.1 %）,SD 7例（18.4 %）,总有效（CR+PR）率81.6 %。治疗结束后CR 32例（84.2 %）,PR 5例（13.2 %）,SD 1例（2.6 %）,总有效率 97.4 %。结论　TPF诱导化疗加DDP同期放化疗是治疗晚期鼻咽癌的可行方案,推荐使用同期DDP 3周化疗方案。剂量强度可否提高,有待进一步研究。     

A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer.

A total of 92 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5) (PE) or cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5)/ifosfamide (2 g/m2, days 1, 2, 3) (PEI) combination chemotherapy. After 2 courses of chemotherapy, patients with limited disease (LD) received chest irradiation of 40-50 Gy. Of the 89 patients who could be wholly evaluated, the overall response rate was 78% for PE and 74% for PEI therapy (NS). For all patients the complete response (CR) rates were 14 versus 21%, respectively, and 22 versus 30% for LD. However, the median survival times for all patients were 55 weeks for PE therapy versus 56 weeks for PEI therapy (NS). The 2-year survival rates were 15 and 17%, respectively, for all patients (NS). There was no difference in the duration of response between PE and PEI therapy in cases with CR or partial response. However, severe leukopenia (< 2,000/mm3) occurred more often after PEI (73%) than after PE (44%) therapy (p < 0.05). These results suggest that PEI is not superior to PE chemotherapy in SCLC. The use of ifosfamide in multimodality treatment regimens needs to be studied further.     

Weekly docetaxel treatment for head and neck cancer

A pilot study was conducted to evaluate the safety and efficacy of weekly docetaxel(DOC) treatment for head and neck cancer as compared with those of 3-weekly DOC treatment at 60 mg/m(2).Weekly DOC was administered at doses ranging from 25-30 mg/m(2)/wk (mean dosage, 40 mg/body/wk) for 3 weeks followed by a 1-week rest or for 6 weeks followed by a 2-week rest. Weekly DOC was administered to 18 patients (1 of whom received prior chemotherapy), and 3-weekly DOC was administered to 29 patients (10 of whom received prior chemotherapy). The overall response rate was 22.2% in the weekly DOC group and 47.8% in the 3-weekly DOC group. In advanced or recurrent cancer, the overall response rate plus long NC (stable disease for at least 6 months) rate was 40.0% in the weekly DOC group, and 42.9% in the 3-weekly DOC group. Only 1 (5.6%) case of grade 3 mucositis developed in the group receiving weekly DOC, while 12 cases of grade 3 or 4 neutropenia (41.4%) and 2 of grade 3 or 4 thrombopenia (6.9%) developed in the 3-weekly DOC group. Based on these results, weekly DOC treatment appears to be useful and feasible for outpatients with head and neck cancer, even in high-risk and elderly patients.     

A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer.

MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.     

Combined modality treatment of short duration in small cell lung cancer

Fifty-seven patients with small cell lung cancer (SCLC) (limited disease = LD in 23, extensive disease = ED in 34) received the combination of CCNU, cyclophosphamide, vincristine and methotrexate (CCOM). A mean number of only 6 (range 1–17) courses of chemotherapy were given. All LD patients received consolidation locoregional radiation (30 Gy) after two courses of chemotherapy. A complete response (CR) was obtained in 61% of LD and 12% of ED patients, and a partial response in 22 and 35% respectively. Median survival was 54 and 34 weeks for LD and ED respectively. Five LD patients survived more than 2 yr, three of them remaining disease-free 4 yr after the cessation of treatment. A subset of 12 LD patients achieving a CR after two courses of chemotherapy was randomized to receive maintenance chemotherapy or observation only after the consolidation radiotherapy. In this small-sized randomized trial maintenance treatment showed a significant decrease of the patients' quality of survival compared to no maintenance treatment. We conclude that combined modality treatment of short duration proved effective in SCLC. Future randomized studies are necessary to show whether prolonged chemotherapy has a meaningful impact on survival, or otherwise the resulting morbidity will plead against it.     

Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.     

Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer

Fifty-two previously untreated patients with small-cell lung carcinoma (SCLC) were treated with a combination of carboplatin 300 mg/m2 intravenously (IV) on day 1 and etoposide 100 mg/m2 IV on days 1 through 3 every 28 days for four courses. Patients with limited disease (LD) subsequently received thoracic radiotherapy; no prophylactic cranial radiotherapy was used. Forty-four patients (85%) achieved an objective response, including 82% (29% complete remissions) of LD patients and 88% (13% complete remissions) of extensive-disease (ED) patients. Median response duration for LD patients was 7 months and 5.5 months for ED patients. Median survival for both LD and ED patients was 9.5 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3/4 leucopenia occurring in 44% of patients. There was one (2%) treatment-related neutropenic death. Treatment was otherwise well tolerated, and in particular no renal toxicity, neurotoxicity, or ototoxicity was seen. This new combination is highly active in terms of response rate, but response duration and survival is disappointing, and might be improved by prolonged treatment or by the use of additional drugs in combination.