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)     

Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.     

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.     

Cisplatin,doxorubicin, cyclophosphamide,and etoposide combination chemotherapy for small-cell lung cancer

Summary Because of potential synergistic interactions, we added 25 mg/m² i. v. cisplatin (P) 25 given on days 1–5 to the combination of 45 mg/m² i. v. doxorubicin (A) given on day 1, 800 mg/m² i. v. cyclophosphamide (C) given on day 1, and 50 mg/m² i. v. etoposide (E) given on days 1–5. The resulting PACE regimen was given every 21 days for the first three courses and then every 28 days for the next five courses. PACE was used in two trials: the first, for both limited and extensive disease, was conducted at the University of Maryland Cancer Center and North Shore University Hospital; and the second, for extensive disease, was carried out as a Cancer and Leukemia Group B pilot study. Chest irradiation was not used. Prophylactic cranial irradiation at a dose of 3,000 cGy was given to all patients achieving a complete response (CR). A total of 33 subjects were entered in the first study; 8 of the 15 (53%) presenting with limited disease and 7 of the 18 (39%) exhibiting extensive disease achieved a CR. A partial response (PR) was obtained in 27% and 33% of cases, respectively. Of the 34 patients entered in the second study, 25 were cligible; 8 (32%) achieved a CR and 6 (24%) showed a PR. Toxicity was severe in both studies, including >90% severe or life-threatening leukopenia and thrombocytopenia. Serial creatinine-clearance evaluations in the first study indicated progressive deterioration, which required discontinuation of the cisplatin before the planned completion of treatment in most cases. Since the response rate was no higher than the historic data reported for the three-drug ACE combination and because the toxicity was severe, the studies were stopped and patients were followed for survival. After a follow-up period of <6 years, the median survival was 24 months for limited disease, with 33% and 27% of the patients being alive at 3 and 6.5 years, respectively. The median survival for extensive disease was 15 and 11 months in the first and second studies, respectively. These pilot studies suggest that the addition of cisplatin may augment the activity of the ACE regimen, but at the cost of severe toxicity. Further studies seem warranted if the myelotoxicity can be better controlled.     

Carboplatin and continuous infusion 5-fluorouracil for advanced head and neck cancer

Fifty-one patients with recurrent or advanced squamous cell carcinoma of the head and neck received carboplatin 70 mg/m²/day bolus × 5 days i.v. and 5-fluorouracil (5-FU) 1000 mg/m²/day by continuous infusion i.v. for 5 days as initial chemotherapy. There were four complete responders (CR) and 12 partial responders (PR). Durations of CR were 6.8 months, 7.2+ months and 14.8+ months with one patient lost to follow up after achieving CR. For objective responders the median relapse-free survival from the time of response was 5.3 months and survival from registration 11.7 months. The median survival for all patients was 4.8 months. The major toxicities were myelosuppression and mucositis. Neutropenia (<1.0 × 10⁹/l) occurred in 19% of patients, thrombocytopenia (<50 × 10⁹/l) in 17% and severe (WHO grade three or four) mucositis was experienced by 28% patients. This combination had less gastrointestinal and nephrotoxicity than platinum containing combinations and can be used in patients with a poorer performance status.     

Safety and efficacy of combination therapy with fludarabine, mitoxantrone, and rituximab followed by yttrium-90 ibritumomab tiuxetan and maintenance rituximab as front-line therapy for patients with follicular or marginal zone lymphoma

BackgroundWe conducted a single-institution phase II clinical trial evaluating the safety and efficacy of combination chemoimmunotherapy followed by radioimmunotherapy consolidation and rituximab maintenance as front-line treatment in indolent lymphomas.Patients and MethodsWe enrolled 20 patients with intermediate- to high-risk follicular lymphoma and 2 patients with marginal zone lymphoma. Treatment consisted of 4-6 cycles of FM (fludarabine 25 mg/m² on days 1-3, mitoxantrone 12 mg/m² on day 1 of each 28-day cycle). The protocol was amended after enrolling the first 4 patients to include rituximab 375 mg/m² on day 1. After 6-8 weeks, responders received ⁹⁰Y-ibritumomab tiuxetan (Zevalin) followed by maintenance rituximab (375 mg/m² weekly × 4 doses, repeated every 6 months for 2 years).ResultsAfter R-FM, the overall response rate was 95% with a complete response rate (CR) of 45% (n = 10), a partial response (PR) rate of 50% (n = 11), and stable disease in 1 patient. Nineteen patients received ⁹⁰Y-ibritumomab tiuxetan with a 60% conversion rate of PR to CR, resulting in an improved CR of 79% (n = 15) and a PR of 21% (n = 4). Fifteen patients proceeded to rituximab maintenance resulting in 3 patients with PR converting to CR. At median follow-up of 49.6 months, median progression-free survival (PFS) was 47.2 months and median overall survival (OS) was not reached in an intent-to-treat analysis. The most common adverse effects were hematologic, with 2 patients experiencing treatment-related myelodysplastic syndrome (MDS), evolving to acute myelogenous leukemia (AML) in 1 patient.ConclusionR-FM with ⁹⁰Y-ibritumomab tiuxetan consolidation and rituximab maintenance is well tolerated, improving CR rates and maintaining durable responses in patients with untreated indolent lymphomas.     

Doxorubicin,cyclophosphamide and VP16-213 (ACE) in the treatment of small cell lung cancer

Summary Small cell lung cancer requires aggressive combination chemotherapy. The three active agents, doxorubicin (A) 45 mg/m² i.v. day 1, cyclophosphamide (C) 1.0 mg/m² i.v. day 1 and VP16-213 (E) 50 mg/m²/day i.v. days 1–5 were given together. The combination (ACE) was given every 21 days without chest irradiation. One hundred and seventy-four patients have been stratified for extent of disease and randomized on three sequential studies testing ACE vs ACE + MER immunotherapy (38 patients), or ACE vs ACE alternating with CCNU, methotrexate, vincristine and procarbazine (109 patients), or ACE vs ACE II (ACE with continuous VP16-213-100 mg/m²/dayx5 days-27 patients-ongoing). The immunotherapy and the alternating non-cross resistant combination have not proven beneficial with respect to response or survival. The ACE combination, regardless of additional treatments, has produced greater than 90% response overall. In limited disease the complete response (CR) frequency is 65%. The median survival for limited disease overall is 14 months and 18 months for patients achieving CR. In extensive disease the CR frequency is 40% with a median survival of 9 months overall and 13 months for patients achieving CR. Response frequency and survival are identical in the first two studies and 20–30% of patients with limited disease are long-term survivors with one late relapse (>3 years). Patients who achieved CR had a significantly longer survival regardless of other factors such as performance status or extent of disease. Prophylactic cranial irradiation was demonstrated to be useful in prevention or delaying CNS metastases in patients who achieved CR. The third generation study of high-dose VP16-213 infusion seeks to increase the CR frequency. ACE chemotherapy without chest irradiation is a highly effective treatment for all patients with small cell lung cancer and compares favorably with all other studies with or without adjuvant radiotherapy.This investigation was supported in part by PHS Grant Number 1 P50CA 32107-01 awarded by the National Cancer Institute, DHHS     

High-dose cyclophosphamide and VP 16 as late dosage intensification therapy for small cell carcinoma of lung

Summary This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (1 g/m²) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a five-drug induction regimen comprising cyclophosphamide (750–1000 mg/m²), adriamycin (40 mg/m²), VP 16 (100 mg/m²) for 3 days, methotrexate (50 mg/m²) and vincristine (2 mg) (CAVMO). There were 16 patients with limited disease, 8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the 11 patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGy was given to the primary site in 10 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival 11 months), while 3 remain alive and in remission at 11, 11, and 24 moths. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival.     

Cyclophosphamide,vincristine, cisplatin,VP-16 and radiation therapy in extensive small-cell lung cancer

Summary Patients with extensive small-cell lung cancer were given induction chemotherapy consisting of cyclophosphamide, vincristine, cisplatin, and etoposide (COPE) every 3 weeks for four cycles. Responding patients then received chest and elective whole-brain irradiation. Patients presenting with brain metastases received therapeutic brain irradiation during the first cycle of chemotherapy. No maintenance therapy was given, but two late intensification cycles of COPE were given at weeks 24 and 48. Among the 34 evaluable patients, the response rate to induction chemotherapy was 59%, with 10% achieving a complete response (CR) and 49%, a partial response (PR). Of the 18 patients who completed chest irradiation, 3 achieved a CR, producing an overall CR rate of 18%. Five patients completed the projected course of treatment. The median duration of response for all patients was 8 months (range, 2–30+ months) and the median survival was 9 months (range, 1–30+ months). Complete responders had a median response duration of 9 months and a median survival of 11 months. This regimen produced significant myelosuppression, with 5 neutropenic deaths (13%) occuring in the 38 patients evaluable for toxicity; an additional 16% required hospitalization for fever while neutropenic. Only six patients (13%) had nadir platelet counts of <50,000/mm³ with no episodes of thrombocytopenic hemorrhage. Nausea, vomiting, and neurotoxicity were mild to moderate in all patients. One patient with no evidence of disease died of radiation pneumonitis at 6 months. While producing significant toxicity, this regimen did not result in a CR rate or survival advantage that would suggest its superiority over standard regimens for small-cell lung cancer.This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA-20319, CA-37981, CA-13612, CA-22411, CA-12213, CA-32102     

Combination of topotecan and cisplatin in relapsed patients with small cell lung cancer: a phase II study of the hellenic cooperative oncology group (HeCOG)

Purpose: To assess the safety and efficacy of a 3-day schedule of cisplatin and topotecan in patients with recurrent small-cell lung cancer (SCLC). Methods: Thirty-four relapsed patients were treated with cisplatin 20 mg/m² and topotecan 0.9 mg/m², both given on days 1–3 every 3 weeks, in a phase II study. Results: Complete response (CR) was achieved in two patients (6%), partial response (PR) in 4 (12%), stable disease in 6 (18%) and progressive disease in 14 (41%). Eight patients (23%) were non-evaluable for response. Among 21 sensitive patients, 2 (9.5%) achieved CR and 3 (14%) PR. Among 13 refractory patients, none achieved CR and only 1 (8%) PR. Median survival was 6.5 months for all patients, 7.8 for sensitive and 6.2 for refractory. Median time to progression (TTP) was 4.4 months for all patients, 5.9 for sensitive and 3.2 for refractory. Grade 3–4 toxicities included anemia (15%), thrombocytopenia (15%), neutropenia (42%), nausea/vomiting (3%), and alopecia (6%). No toxic death occurred. Conclusions: This 3-day schedule was well tolerated, produced modest response rates but good survival and TTP both in sensitive and refractory patients with relapsed SCLC.     

The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis

Purpose We developed a laboratory based regimen called GTX which induces synergistic apoptosis in human pancreatic cancer cells. This retrospective review summarizes our clinical experience with GTX in an initial group of 35 patients; 66% untreated and 34% failed prior therapies. Methods All patients treated with GTX for metastatic pancreatic cancer, prior to initiation of a prospective phase II trial of GTX were assessed and followed until death. GTX consisted of capecitabine (X), 750 mg/m² p.o. BID on days 1–14, gemcitabine (G) (750 mg/m²) over 75 min and docetaxel (T) (30 mg/m²) on days 4 and 11. Thus one cycle of GTX was 14 days with 7 days off for a 21 day cycle. Tumor assessments were repeated every 3 cycles. Results All 35 patients had metastatic pancreatic cancer (94% liver, 6% lung sites). Grade 3–4 hematological toxicities were: leukopenia and thrombocytopenia—both 14%, and anemia 9%, respectively. The overall response rate of all 35 patients treated with GTX (from 0.5 cycles onward) was 29% (CR/PR) by WHO criteria, and 31% had a minor response or stable disease (MR, SD). At the metastatic sites for the 35 patients, there were 9% complete (CR) and 31% partial (PR) responses (total 40%). For the 31 patients who had their primary tumor (4 patients had a prior Whipple resection), there were 13% CR and 19% PR for a response rate of 32% at the primary tumor site. Overall median progression free survival of responders was 6.3 months (95% C.I. 4.4–10.4 months) and median survival was 11.2 months (95% C.I. 8.1–15.1 months). Survival after initiation of GTX at 12, 18, 24 and 30 months was 43, 29, 20, and 11%, respectively. Conclusion Our retrospective review suggests that GTX has potential as a regimen for untreated and treated metastatic pancreatic cancer. An erratum to this article can be found at     

Vincristine,adriamycin, cyclophosphamide,and etoposide (VP16-213) in small-cell anaplastic carcinoma of the lung

Summary Twelve patients with small-cell anaplastic carcinoma of the lung were treated with vincristine 1 mg/m² i.v. day 1, adriamycin 50 mg/m² i.v. day 1, cyclophosphamide 1,000 mg/m² i.v. day 1, and etoposide 80 mg/m² i.v. day 2, 4, 6 given on an outpatient basis and repeated at 3-week intervals. As consolidation therapy seven patients received two courses of BCNU median 29 mg/m² (range 24–73 mg/m²) short term intraarterial infusion in the bronchial artery with 2 to 3-weeks intervals.One patient with limited disease had no evidence of disease for 13+ months and one patient complete remission for 3+ months. Four of ten patients with extensive disease had complete remission for median 5 months (range 2+ to 5+ months) and four patients had partial remission for median 5 months (range 4 to 5+ months). Despite side effects the chemotherapy was well tolerated by the patients.The results correspond to those obtained with other effective regimens in small-cell anaplastic carcinoma of the lung.     

Ifosfamide,mitomycin and radiotherapy in non-small-cell lung cancer

Summary Ifosfamide and mitomycin C are two of the more active single agents in non-small-cell lung cancer (NSCLC). This study evaluates these drugs in combination followed by radiotherapy. A total of 33 ambulatory patients with inoperable NSCLC were treated with 5 g/m² ifosfamide as a 24-h infusion, with the concurrent administration of sodium 2-mercaptoethane sulphonate (mesna; 160% of the ifosfamide dose) and 6 mg/m² mitomycin C given as an i.v. bolus injection on the 2nd day. The median age of the patients was 61 years. In all, 20 patients had limited disease and 13, extensive disease. A total of 30 were assessable for response to chemotherapy, 8 of whom achieved a partial response (PR) and 5, a complete response (CR) (2 were verified bronchoscopically). The overall response rate was thus 43%. All but one response (a PR) were in patients with limited disease (LD). A total of 21 patients, including 13 responders, received thoracic irradiation (30 Gy in 8 fractions over 10 days) following chemotherapy. One PR was converted to a radiological CR. In all, 17 (55%) of the patients were alive at 1 year. All patients suffered chemotherapy-induced alopecia (WHO grade 3), but there were no treatment modifications due to myelosuppression, haemorrhagic cystitis or other toxicity. WHO grade 3 nausea and vomiting were seen in all patients. There was one treatment-related death. Combination therapy using ifosfamide and mitomycin C has useful activity in NSCLC.     

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer

Aim The irinotecan–cisplatin combination has emerged as a new standard for the treatment of advanced-stage small-cell lung cancer (AS-SCLC). To move forward we developed a 3-day regimen of cisplatin, etoposide and irinotecan.Methods Successive cohorts of AS-SCLC patients were treated with irinotecan administered as a single 1-h infusion in combination with fixed doses of cisplatin (20 mg/m²) and etoposide (75 mg/m²), both given for three consecutive days (ECI regimen). Irinotecan dose was escalated from 60 mg/m² by 40-mg/m² increments. At mid-step between the maximum tolerated dose (MTD) and the previous dose level, patients were randomized for the day of administration of irinotecan (day 1 vs day 3).Results A total of 36 AS-SCLC patients received 166 courses of treatment at four dose levels. The MTD of irinotecan was 140 mg/m² (three dose-limiting toxicities, DLTs), and the recommended optimal dose (ROD) 120 mg/m² (two DLTs). DLTs were febrile neutropenia and grade 3 diarrhea. Other toxicities were mild. No difference in toxicity was seen between the two time schedules. A 77% (95% CI 63.25–90.75%) response rate was recorded among 31 evaluable patients and the median survival was 12 months.Conclusions The ECI regimen was well tolerated and showed considerable activity in patients with AS-SCLC. Phase II/III evaluation is ongoing.The results of this trial were presented at ECCO 12, Copenhagen, Denmark, September 2003.     

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer

Background: We conducted a phase I/II trial to assess the feasibilityand activity of combination chemotherapy with etoposide, ifosfamide,cisplatin, and epirubicin in limited-stage (LS, stage I–IIIB) andextensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-pointswere treatment-related morbidity and mortality, response rate, duration ofresponse, and survival.Patients and methods: Chemotherapy followed by granulocytecolony-stimulating factor was given at a dose of etoposide (500mg/m²), ifosfamide (4000 mg/m²), cisplatin (50mg/m²), and epirubicin (50 mg/m²) (VIP-E) to107 patients with NSCLC. Twenty-five patients with qualifying responsesproceeded to high-dose chemotherapy with autologous peripheral blood stem celltransplantation after etoposide (1500 mg/m²), ifosfamide(12,000 mg/m²), carboplatin (750 mg/m²) andepirubicin (150 mg/m²) (VIC-E) conditioning.Results of conventional-dose VIP-E: 35 of 102 (34%) evaluablepatients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed nochange (NC); the remainder of patients progressed with therapy (PD). Objectiveresponse rate was 68% (4% CR, 64% PR) in LS-NSCLC and23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration ofsurvival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-yearsurvival was 26% in LS and 2% in ES-NSCLC.Results of high-dose VIC-E: 23 of 24 evaluable patients improved ormaintained prior responses (92%), 1 patient showed NC. Treatmentmortality was 4%. Median duration of survival was 17 months in LS-NSCLCand 10 months in ES-NSCLC. Two-year survival was 30% in LS and8% in ES-NSCLC.Conclusion: Response-rates and survival after conventional-dose VIP-Echemotherapy are comparable to other published trials of combinationchemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage,but unacceptably high in extensive stage NSCLC. Although better response-rateswere achieved in the high-dose arm, they did not translate into improvedsurvival. Most stage IV NSCLC-patients will neither benefit from VIP-Econventional dose, nor from VIC-E high dose chemotherapy. Whether selectedLS-patients with partial or complete responses to VIP-E induction chemotherapycould benefit from dose intensification in an adjuvant or neo-adjuvant settingremains to be determined.     

Three Conventional-Drug Combination (Ifosfamide,Carboplatin, Etoposide - ICE Regimen) in Advanced Non-Small Cell Lung Cancer (NSCLC)

Abstract

Fifty consecutive patients with stage IIIB-IV non-small cell lung cancer (NSCLC) received the ICE regimen at intermediate doses (ifosfamide 1 g/m², carboplatin 120 mg/m², etoposide 80 mg/m², day 1 to 3, q.4 weeks, for a maximum of 6 cycles). Overall 2 complete response (CR) and 10 partial response (PR) (overall response, OR: 24%, 95% C.I. 14-37%) were observed. An additional 7 patients had stable disease (SD) lasting more than 6 months, therefore a clinical benefit (CR+PR+SD >6 mos) was achieved in 19 patients (38%). Median time-to-progression (TTP) was 7 months and median overall survival (OS) was 11 months; 1- and 2-year survival rates were 36% and 10%. The ICE regimen was well tolerated and devoid of any cardiac, hepatic or neurologic toxicity. Moderate nausea and vomiting were easily manageable, grade 2 alopecia was universal, while hematological toxicity was mild (grade 2 leuko-and thrombocytopenia). Due to its efficacy and safety profile, this 3-drug regimen can be considered for routine community use.     

Etoposide and split-dose cisplatin in small-cell lung cancer

Forty-seven untreated patients with small-cell lung cancer (SCLC) were treated with a combination of etoposide (170 mg/m2 intravenously, i.v., days 3-5) and cisplatin (50 mg/m2 i.v., days 1 and 7). Responding patients with limited disease received four cycles followed by irradiation (delivered to the primary site, mediastinum, and supraclavicular region) with 50 Gy. Prophylactic cranial irradiation (PCI) with 30 Gy was performed in patients who achieved complete remission. Responding patients with extensive disease received four to six cycles of chemotherapy. The overall objective response rate (complete response plus partial response, CR + PR) was 94% (44 of 47). CR rate (all patients) was 57% (27 of 47), 51% (19 of 37) in extensive disease and 80% (8 of 10) in limited disease. The median remission duration is 13 months (12 months in extensive disease and 26 months in limited disease). The median survival is 16 months for all patients (15 months in extensive disease, 28 months in limited disease). Mean follow-up is 13 months. Toxicity was primarily hematologic. Twelve of 47 patients had leukopenia of WHO grade 4, 30 of 47 of grade 3. Thrombocytopenia of WHO grade 3 and 4 occurred in 6 of 47 and 2 of 47 patients, respectively. There were four severe infections in neutropenic patients, but no chemotherapy-related lethal complications. The only treatment-related death was that of one patient who died in CR of progressive neurologic dysfunction 11 months after PCI. This schedule of etoposide and cisplatin induces high CR rates and a prolonged survival, especially in patients with extensive disease.     

Mitomycin C treatment of advanced,hormone-resistant prostatic carcinoma: a phase II study

Summary From February 1984 to February 1987, 29 patients with advanced, hormone-resistant prostatic carcinoma were treated with mitomycin-C at a dose of 20 mg/m² every 6 weeks (15 mg/m² in patients >75 years old and in those who had undergone previous radiotherapy). In the 27 evaluable patients, there were no complete remissions (CR), 2 partial remissions (PR), 14 stabilizations (STAB), and 11 cases of progressive disease (PRO). Ten stabilized patients showed significant pain reduction. Toxicity was minimal. The actuarial median survival was 10.8 months. In this study, mitomycin C was not active in terms of CR+PR; however, a beneficial symptomatic effect was frequently observed.     

Combination of topotecan and etoposide as a salvage treatment for patients with recurrent small cell lung cancer following irinotecan and platinum first-line chemotherapy

Purpose The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. Patients and methods From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan 1 mg/m² (day 1–5) and etoposide 80 mg/m² (day 1–3). Treatment was repeated every 21 days for a maximum of 6 cycles. Results Twelve patients were refractory to first-line chemotherapy. Seventeen patients (73.9%) were male and the median age was 63 years. ECOG performance status was 0–1 in 13 (56.5%) patients. The median cycles of chemotherapy was three. Twenty-one patients were assessable for response evaluation. The overall response rate was 17.4% (0 CR, 4 PR, 7 SD, 10 PD) under the intent-to-treat analysis. Two sensitive case patients and two refractory case patients achieved partial response. After a median follow-up of 20.8 months, median progression free survival was 4.7 months and median overall survival was 9.5 months. The estimated 1-year survival rate was 38.7%. All patients were assessable for toxicity and major toxicities were myelosuppression. Grade 3/4 neutropenia and thrombocytopenia occurred in 18 (78.3%) and 12 (52.2%) patients, respectively. Grade 3/4 febrile neutropenia occurred in two patients (8.7%) and infection in three patients (13.0%). There was one treatment-related death due to pneumonia. Conclusion This salvage regimen showed modest efficacy and manageable toxicities. Further study will be required in recurrent SCLC patients pretreated irinotecan and platinum.     

Extensive stage small cell carcinoma of the bronchus

Summary Fifty-four patients whose disease had been staged as extensive small cell carcinoma of the bronchus were randomised to receive either CAV¹ (cyclophosphamide 600 mg m^-2 i.v., adriamycin 50 mg m^-2 i.v., given on day 1, and etoposide 500 mg m^-2 p.o. given on day 3) or CAV⁵ (cyclophosphamide and adriamycin given as for CAV¹, etoposide 500 mg m^-2 given in divided dose over days 3–7) on a 21-day schedule. The two regimens proved comparable (CR+PR 55% vs 56%), and the survival curves were virtually superimposable (median survival: CAV¹, 8 months; CAV⁵, 9 months). Only five patients are still alive. The toxicity of the two treatments was similar. The scheduling of etoposide over 1 or 5 days seemed clinically unimportant in this study, perhaps because of concurrent use of other effective chemotherapy drugs.