Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen

PURPOSE:: Results of a multidrug chemotherapy regimen consisting of cyclophosphamide,pirarubicin, teniposide, and prednisolone (CTVP) plus subcutaneousgranulocyte colonystimulating factor (G-CSF) in elderly patientswith aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS:: Between January and December 1992, 46 previously untreated patientsolder than 69 years with intermediate- and high-grade NHL receivedcyclophosphamide 750 mg/m², teniposide 75 mg/m², pirarubicin50 mg/m² day 1, and prednisolone 40 mg/m² days 1 to 3. G-CSF,5 µg/kg/day, was administered from day 4 up to day 14or when the absolute neutrophil count reached 5 x 10⁹/1. Sixcycles were scheduled every 3 weeks. RESULTS:: Grade 3 or grade 4 neutropenia complicated 22% and 26% of chemotherapycycles, respectively. Fever or/and clinical infection were observedin 4% and 14% of cycles. One toxic death related to a septicshock occurred. Eight cycles (4%) were delayed with a medianduration of 7 days. Administered median dose intensity was 93.5%.Objective response rate was 74% and 46% of the patients achieveda complete response. The 2-year overall survival and eventfreesurvival rates were 47% and 28%. CONCLUSION:: In comparison with a previous group of patients treated withCTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-inducedmorbidity in an outpatient setting in elderly patients withaggressive NHL without modifying response rate or survival. chemotherapy, elderly, G-CSF, lymphoma     

Carboplatin and 5-fluorouracil in poor performance status patients with advanced urothelial cancer

BACKGROUND: In view of the difficulties in administering aggressive treatmentto elderly patients, frequently with concomitant medical problems,a treatment program with the combination of carboplatin and5-FU for advanced urothelial tumors was designed. The aim wasto maintain an efficacious therapeutic schedule while minimizingtoxicity. PATIENTS AND METHODS: Twenty-three patients with advanced bidimensionally measurableurothelial carcinoma were given carboplatin 100 mg/m² and 5-fluorouracil500 mg/m² days 1–3 which was escalated to carboplatin125 mg/m² and 5-fluorouracil 625 mg/m². 5 patients were >70 years, the ECOG performance status was 2–3 in 10 patients(43%), and the creatinine was > 2.0 mg/dl in 3 patients (13%).Five patients (22%) had pre-existing cardiac disease, and Ihad hepatopathy. Nine patients (39%) had prior cisplatin. RESULTS: Ten patients remained at level 1, and 12 others had the dosageescalated to level 2. Twenty-one patients are evaluable forresponse. Response was observed in 5 of 21 (24%) evaluable patients(95% confidence limits 15%–33%), only at dose level 2.There was 1 CR (5%) and 4 PR (19%). There were no responsesin patients who had prior DDP versus 5 of 13 (38%) responsesin patients who had not had prior DDP. The median time to responsewas 2 months. The median duration of response was 8 months.At level 2 myelotoxicity was significant, and led to a returnto level 1 in 2 patients. Nine of 12 patients (75%) treatedat level 2 had grade 3 leukopenia, and 1 patient had nadir sepsis.4 patients (33%) had grade 4 thrombocytopenia. CONCLUSIONS: Moderate activity was shown with this regimen in untreated patientsat level 2. This regimen presents a feasible outpatient alternativefor patients who are unable to undergo more aggressive chemotherapy. carboplatin, chemotherapy, poor performance status, transitional cell carcinoma, urothelium     

Accelerated chemotherapy with high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF in locally advanced and metastatic breast cancer

BACKGROUND: This study evaluated the toxicity of high-dose epirubicin andcyclophosphamide plus r-met-HUG-CSF (G-CSF) given every 2 weeksand compared the dose-intensity achieved with this schedulewith that obtained in a previous study we conducted in whichthe same regimen was given every 3 weeks without G-SCF (EC 21).The secondary objective was to explore the activity of thisregimen. PATIENTS AND METHODS: Between December 1991 and March 1994, 41 patients (pts), 19with locally advanced breast cancer (LABC) and 22 with metastaticbreast cancer (MBC), were given high-dose epirubicin (Hd-Epi)(120 mg/m²) and cyclophosphamide (CTX) (600 mg/m²) on day 1every 14 days (EC 14) plus granulocyte colony-stimulating factor(G-CSF) (5 µg/kg/d s.c. on days 2–12). A total of8 cycles in LABC pts (4 pre- and post-surgery), and 6–8cycles in MBC pts were administered. The results were comparedwith those obtained in the previous study. RESULTS: The incidence of WHO grade 3–4 neutropenia was significantlyreduced in te EC 14 + G-CSF regimen (25.2% vs. 46.8% in 214and 250 evaluable cycles, respectively, p< 0.0001), as wellas the incidence of neutropenic fever (7% vs. 3%, p = 0.05).Grade 3–4 anemia (36.6% vs. 8% pts, p = 0.001) and grade3–4 thrombocytopenia (17.1% vs. 0 pts, p — 0.002),were significantly more frequent in EC 14 +G-CSF. No significantdifferences in the other side effects were found.A total of17 of 207 of the cycles (8.2%) were delayed in the EC 14 + G-CSFvs. 58/271 (21.4%) in the EC 21 (p< 0.0001). The main reasonsfor these treatment delays were neutropenia (1% vs. 15%), anemia(3% vs. 0) and thrombocytopenia (1% vs. 0).As a result of treatmentacceleration and differences in dose delays, the patients onEC 14 + G-CSF received a higher dose-intensity (Epi 58.51 mg/m2/wkvs. 36.8 mg/ m7wk; CTX 292.52 mg/m2/wk vs. 182.9 mg/m2/wk).A complete response at surgery was obtained in 9/19 (47.4%)LABC pts. An objective CR was obtained in 11/22 MBC pts (50%)and a partial response in 8/22 (36.4%), yielding an verall responserate of 86.4%. CONCLUSIONS: Hd-Epi + CTX is very active against both LABC and MBC. The administrationof G-CSF allows dose intensification of both drugs (a 59.5%increase of the actual dose intensity) with acceptable clinicaltolerance (a lower incidence of neutropenia but a higher incidenceof anemia and thrombocytopenia). Only a specifically designedphase III trial will lead to definitive conclusions regardingthe greater antitumor activity of accelerated CSF-includingregimens as compared to standard chemotherapy for advanced breastcancer. advanced breast cancer, dose intensity, high-dose epi, rh G-CSF     

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: I. A randomized dose escalation and feasibility study with bi- and tri-weekly regimens

Background: To determine the maximum tolerated dose of a bi-and tri-weekly combination chemotherapy with cyclophosphamide,doxorubicin, vincristine and prednisone plus etoposide (CHOEP)regimen without stem-cell support. Patients and methods: Randomized phase I/II multicenter four-level(cyclophosphamide: 1000–1200–1400–1600 mg/m²;doxorubicin: 55–60–65–70 mg/m²; etoposide:375–450–525–600 mg/m²) dose escalation studywith CHOEP-14 and CHOEP-21 in young patients (18–60 years)with newly diagnosed aggressive non-Hodgkin's lymphoma. Dose-limitingtoxicity was defined as thrombocytopenia <80 000/mm³ andleukocytopenia <2500/mm³ on days 16 (CHOEP-14) and 23 (CHOEP-21)or prolonged (>4 days) leukocytopenia (<1000/mm³) or thrombocytopenia(<20 000/mm³). Results: One hundred and thirty-nine patients (high-CHOEP-14:47, high-CHOEP-21: 92) were randomly allocated to the study.Maximal tolerated dose was level 2 for CHOEP-14 and level 4for CHOEP-21. With a less favorable profile of patients in CHOEP-14,4-year event-free survival was 47.9% after high-CHOEP-14 and66.2% after high-CHOEP-21, 4-year overall survival 62.1% afterhigh-CHOEP-14 and 73.4% after high-CHOEP-21, respectively. Conclusion: Significant dose escalations of CHOEP are possiblewith granulocyte colony-stimulating factor support, with differentchemotherapy models favoring the maximally escalated bi- ortri-weekly regimen, respectively. Because a higher total dosecan be achieved with six cycles of the tri-weekly compared withthe biweekly regimen, CHOEP-21 at dose escalation level 3 waschosen for a nationwide randomized comparison with baselineCHOEP-21 in a subsequent phase III trial. Key words: aggressive NHL, chemotherapy models, clinical trials, dose escalation     

多西紫杉醇与多西紫杉醇联合卡铂治疗老年晚期非小细胞肺癌的疗效观察

目的比较单药多西紫杉醇（Docetaxel,TXT）和TXT联合卡铂（Carboplatin,CBP）即TC方案治疗老年晚期非小细胞肺癌(Non-small cell lung cancer,NSCLC)的疗效及不良反应的差异。方法46例晚期NSCLC老年患者,随机分为两组: TXT组给予TXT 50mg/m²,第1天,每2周重复;TC组给予TXT 40mg/m²,第1天, CBP 300mg/m²,第1天,每2周重复。结果两组有效率(36.4% vs 41.7%, P=0.77)和中位生存期(9.2月 vs 7.9月,P=0.13)差异均无统计学意义。TXT组患者生活质量改善优于TC组（77.3% vs 45.8%,P=0.03）,且Ⅲ+Ⅳ度白细胞减少发生率明显低于TC组（18.2% vs 54.2%, P=0.02）。两组非血液学毒性较温和,耐受性良好。结论与TC方案相比,TXT单药2周方案治疗老年NSCLC疗效相当,耐受性及生活质量更好,值得临床进一步观察研究。     

Phase I study of the novel distamycin derivative tallimustine (FCE 24517)

BACKGROUND: Tallimustine, a benzoyl nitrogen mustard derivative of the antiviralagent distamycin A, is a new alkylat-ing agent which binds toA-T rich regions of DNA in the minor groove producing highlysequence-specific alkylations. Its main preclinical featuresare a significant antitumour activity in animal models and alack of cross-resistance in vitro and in vivo with L-PAM. Myelotoxicitywas dose-limiting in animals, with a more than 100-fold differencein bone marrow sensitivity between mice and dogs. PATIENTS AND METHODS: Forty adult patients (pts) with solid malignancies were enteredin the study. The drug was administered as an IV bolus every4 weeks. CBC was repeated twice a week and serial assessmentsof renal function were performed in the week following the firstcycle. From the starting dose of 50 µg/m², correspondingto 1/3 of the highest non-toxic dose (HNTD) in dogs, there wereincreases through 10 dose levels, with reliance only on thefeatures of the myelotoxicity observed. RESULTS: The main toxic effect was neutropenia which was dose-limiting,selective and short-lasting. Only previously-untreated pts receiveddoses of 750 µg/m² or more, withgrade 4 neutropenia occurringin     

Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and antiretroviral therapy in HIV-related non-Hodgkin's lymphoma

BACKGROUND:: A phase I/II trial determined the maximum tolerated dose (MTD)of CEOP for AIDS-related non-Hodgkin's lymphoma (NHL) with concurrentfilgrastim and antiretroviral therapy. PATIENTS AND METHODS:: Fourteen AIDS-NHL patients, chemotherapy-naïve and ECOGperformance status >2 received filgrastim 1.0 µg/kgs.c. daily for 3–7 days to assess neutrophil response,followed by CEOP with filgrastim support 10 µg/kg s.c.daily, day 2–14, continued if the absolute neutrophilcount (ANC) <1.2 x 10⁹/l. Two CEOP dose cohorts were used:cohort 1 (5 patients) - cyclophospharnide (C) 500 mg/m², epirubicin(E) 37.5 mg/m², vincristine (O) 2 mg and prednisolone (P) 75mg/m² daily on days 1–5; cohort 2 (9 patients) - C 750mg/m², E 50 mg/m², same doses of O and P. Antiretroviral therapywas maintained (zidovudine-10, ddI-3, both-1). RESULTS:: In cohort 1, 4/5 patients received at least 3 courses of CEOPwith one complete response after five cycles and four progressions.Four have died (3–21 months after entry) with 1 aliveat 40 months. Dose limiting toxicity (DLT - grade IV febrileneutropenia in cycle 1) occurred in 1 patient. In cohort 2,5/9 completed 5 cycles with 6 complete responses, 1 partialresponse and 2 progressions, 6 deaths and 3 alive at 33 months.DLT (evaluable in 8 patients) occurred in two patients. Mediansurvival for both cohorts was 17 months. Mean relative doseintensity was >85%. CONCLUSIONS:: The dosages of CEOP in cohort 1 defined the MTD however thecohort 2 doses with filgrastim and antiretroviral therapy gavean encouraging response, acceptable toxicities and merit furtherstudy. AIDS, antineoplastic agents, antiretroviral therapy, G-CSF, non-Hodgkin's lymphoma     

Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer: A Hellenic Co-operative Oncology Group study

PURPOSE:: To compare the efficacy and toxicity of etoposide and cisplatin(EP) with etoposide and carboplatin (EC) in combination withirradiation in small-cell lung cancer (SCLC). METHODS:: Previously untreated patients (pts) with SCLC and measurableor evaluable disease were randomized to receive either cisplatin50 mg/m² on days 1–2 or carboplatin 300 mg/m² on day 1,both combined with etoposide 300 mg/m² on days 1–3 every21 days for 6 treatment cycles. The vast majority of respondinglimited disease (LD) pts and complete responders (CR) with extensivedisease (ED), also received thoracic irradiation (TI) and prophylacticcranial irradiation (PCI) concurrently with the third cycle. RESULTS:: Of the 147 patients registered, 143 were eligible; median performancestatus (PS, WHO) was 1, and tumour stage was LD in 41 pts ofeach treatment group. The mean delay between cycles was 8 daysin the EP group and 9 in the EC group increasing in both armswith the number of treatment courses. The drug dose administeredper unit time as a proportion of the protocol dose was 74% and80% for the two groups respectively. Leukopenia, neutropenicinfections, nausea, vomiting, neurotoxicity and hyperergic reactionswere more frequent and/or severe in the EP group. The CR rateswere 57% and 58% for EP and EC respectively. Median survivalfor all pts was 12.5 and 11.8 months, respectively. CONCLUSION:: Both treatments proved to be effective, with no differencesin response and survival between the two treatment arms. TheEC regimen was associated with significantly less toxicity. small-cell lung cancer (SCLC), cisplatin, etoposide, carboplatin     

Adjuvant capecitabine chemotherapy using a tailored-dose strategy in elderly patients with colon cancer

BackgroundThis study was conducted to analyze the feasibility of adjuvant capecitabine therapy using a tailored-dose escalation strategy in elderly patients with colon cancer (CC).MethodsCC patients (≥70 years of age) who received adjuvant capecitabine were enrolled. The starting dosage of capecitabine was 2000 mg/m²/day (days 1–14, every 3 weeks). On the second cycle, the dosage was escalated to 2500 mg/m²/day if the patient tolerated the first cycle. Dose intensity (DI), toxicity, and the change in quality of life (QoL) were evaluated.ResultsOf 82 patients enrolled, 67 completed eight cycles. Dose escalation to 2500 mg/m²/day was possible in 56 patients, and this dosage was maintained in 24 patients until the completion of chemotherapy (eight cycles). Forty-one patients completed therapy with a DI ≥ 1333 mg/m²/day [relative dose intensity (RDI) ≥ 80%]. Toxic effects were tolerable and the QoL was not compromised during treatment. Creatinine clearance <50 ml/min and Charlson-Age comorbidity index ≥8 were related to a reduced capecitabine dosage (RDI < 80%).ConclusionsA tailored-dose escalation strategy was feasible in elderly CC patients receiving adjuvant capecitabine chemotherapy. Decreased renal function and an increased number of comorbidities were independently predictive of reduced administration of the capecitabine dose.     

Oral fluoropyrimidines (capecitabine or S-1) and cisplatin as first line treatment in elderly patients with advanced gastric cancer: a retrospective study

Background: This study aimed to evaluate the safety and efficacy of oralfluoropyrimidines and cisplatin therapy in elderly patientswith untreated advanced gastric cancer (AGC) retrospectively.In addition, we evaluated the relative activity and toxicityof these agents in this patient population. Methods: Clinical data from 72 patients with previously untreated AGC,who were treated with capecitabine/cisplatin and S-1/cisplatin,were reviewed. Oral fluoropyrimidines were administered orallytwice a day on Days 1–14. The dose of capecitabine was1250 mg/m² and that of S-1 was 50 mg [body surface area (BSA)< 1.5 m³] or 60 mg (BSA > 1.5 m³) twice a day. Cisplatinwas administered intravenously on Day 1 (before the first doseof capecitabine or S-1) at a dose of 70 mg/m² over a 2 h period.The chemotherapy cycle was of 3 weeks (with oral capecitabineor S-1). Results: Thirty-two and 40 patients received the S-1 and capecitabineregimens, respectively, and were included in the analysis. TheS-1 protocol had a response rate of 40.6%, a median time-to-progression(TTP) of 5.4 months and a median survival of 9.6 months. Thecapecitabine had a response rate of 55%, a median TTP of 5.9months and a median survival of 10.2 months. Each protocol hada similar incidence of Grade 3 or 4 adverse events. However,there was a higher rate of the hand–foot syndrome (6 versus37%) and diarrhea (25 versus 32%) in the capecitabine group. Conclusion: Oral fluoropyrimidines and cisplatin in elderly patients withuntreated AGC showed encouraging results. The treatment waswell tolerated with a manageable toxicity profile. The comparisonof S-1 with capecitabine showed that capecitabine had a slightlyhigher response rate (statistically not significant) in additionto a higher rate of adverse events such as the hand–footsyndrome and diarrhea. These data should be warranted with furtherprospective studies.     

Phase II study of cisplatin and 120-hour continuous infusion of 5-fluorouracil in patients with advanced pancreatic adenocarcinoma

BACKGROUND:: Advanced pancreatic carcinoma (APC) is a rapidly fatal diseaseand an active chemotherapy with palliative effects and impacton patient survival is needed. 5 fluorouracil (5-FU) combinedwith cisplatin (CDDP) has a recognized synergjstic activity,but its activity in APC has never been well established. METHODS:: Forty eligible patients (pts) with measurable APC were treatedin a phase II trial with 5-FU 1000 mg/m²/ day from day 1 today 5 by continuous intravenous infusion and CDDP 100 mg/m²on day 2. Eighty percent of the pts (36/40) had metastatic disease,32.5% (13/40) were previously treated and 65% (26/40) had performancestates of 2 or 3. RESULTS:: Of 38 evaluable pts, one had a complete response and 9 achievedpartial responses; the overall response rate (RR) was 26.5%(95% CI: 12% to 40%). The median duration of responses was 10months (range 4-18). The RR in non-pretreated pts was 32% Apalliative effect was seen in 45% of pts (17/38). The mediansurvival was 7 months and 12 pts (29%) were alive at 1 year.Leukopenia was the most important toxicity; 11 pts (27%) hada grade 4 leukopenia and 3 had neutropenic fever. CONCLUSIONS:: The combination of CDDP and 5-FU in continuous infusion seemsan active and well tolerated treatment in APC and will be comparedto standard therapy in a multicentric randomized trial. pancreatic cancer, chemotherapy, 5-fluorouracilcisplatin combination     

Dose-dependent impairment of testicular function in patients treated with cisplatin-based chemotherapy for germ cell cancer

BACKGROUND:: The enormous differences in semen quality following cisplatin-basedcombination chemotherapy reported in previous studies may becaused by differences in the cisplatin dosages. PATIENTS AND METHODS:: We examined thirty-three patients treated with conventional-dosePEB (cisplatin 20 mg/m² x 5, q3w, etoposide 100 mg/m² x 5 q3wand bleomycin 15 mg/m² q1w) and 21 patients treated with high-dosePEB (cisplatin 40 mg/m² x 5 q3w, etoposide 200 mg/m² x 5 q3wand bleomycin 15 mg/m² qlw). RESULTS:: The sperm density was significantly higher (median 5.83 mill/ml)in the conventionally-treated group than in the group of high-dose-treatedpatients (median 0.005 mill/ml) (p = 0.008). Azoospermia waspresent in 19% of the conventionally- and in 47% of the high-dose-treatedpatients. All patients treated with a cumulative cisplatin doseabove 600 mg/m² had severe oligospermia or azoospermia. Serumvalues of basal follicle-stimulating hormone (FSH) (median 27.2iu/l vs. 15.2 iu/l) and stimulated FSH (median 57.7 iu/l vs.28.4 iu/l) were significantly higher in the high-dose groupthan in the conventionally-treated group. No differences couldbe detected in basal or stimulated testosterone or in luteinizinghormone in serum. CONCLUSION:: In patients treated with PEB for testicular cancer, we foundstrong evidence that the impairment of spermatogenesis is dose-dependent. cytotoxic agents, fertility, spermatogenesis, Leydig cell function, testicular cancer     

Minoxidil (Mx) as a prophylaxis of doxorubicin - induced alopecia

BACKGROUND: Minoxidil (Mx) is known to induce hair growth in men with male-patternbaldness. Based on this potential, the effectiveness of Mx 2%topical solution was evaluated in cancer patients (pts) to preventdoxorubicin-induced alopecia. PATIENTS AND METHODS: 48 female pts with different types of solid tumors treated withdoxorubicin-based chemotherapy in a dose range of 50–60mg/m²/cycle were randomly assigned to receive Mx 2% topicalsolution or placebo. RESULTS: 88% and 92% of pts in both arms showed severe alopecia (p –ns). No adverse effects were observed. CONCLUSIONS: In this study Mx 2% topical solution was non-toxic but was noteffective in the prevention of chemotherapy-induced alopecia. alopecia, minoxidil, doxorubicin, chemotherapy     

Dose intensification of cisplatin chemotherapy through biweekly administration

PURPOSE: Dose intensity (DI, expressed in mg/m²wk) may be an importantfactor in the clinical use of cisplatin (DDP). We have exploredthe shortening of the cycle interval as a way to increase theDI of DDP. PATIENTS AND METHODS: DDP 180 mg/m² was given intravenously (i.v.) over 4 hours; sodiumthiosulfate (STS) was given i.v. in the opposite arm at a loadingdose of 4 g/m², followed by 12 g/m² over 6 hours. Each cyclewas repeated every two weeks. Seventy-five cycles were administeredto 28 patients in this clinical trial. RESULTS: In 19 patients who received 2 or more cycles of chemotherapy,a delay of three or more days was required on 17/66 courses(26%); the mean DDP DI actually received by these patients was83 mg/m²/wk (88% of the planned DI). The major side effect wasototoxicity; this occurred in 9 patients (33%), but none requireda hearing aid. Myelosuppression was moderate with thrombocytopeniagreater than neutropenia. Nephrotoxicity (creatinine > 2mg/dl) occurred on only 2 cycles (3%). Three patients (11%)developed symptoms of peripheral neuropathy. In 23 evaluablepatients, the overall response rate was 39%. CONCLUSION: It is feasible to give 180 mg/m² of DDP and STS every two weekswith tolerable nephrotoxicity but without blocking other typesof toxicity, such as myelosuppression and ototoxicity. The shorteningof cycle intervals resulted in a markedly increased DI. biweekly, cisplatin, high-dose intensity chemotherapy     

Combination 5-fluorouracil (FU), folinic acid (FA), and {alpha}-interferon 2B in advanced gastric cancer: Results of a phase II trial

BACKGROUND: Based on encouraging treatment results with FU/FA or FU/IFNin gastrointestinal tract cancer, a phase II study was conductedto evaluate the effects and toxicity of combination FU/FA/IFNin patients (pts) with inoperable/metastatic gastric cancer. PATIENTS AND METHODS: IFN 6 M.U. s.c. 1 x/week, FU 500 mg/m² bolus i.v. 1 x/week andFA 500 mg/m² 1 x/week as a 2-hour infusion. Of 72 treated pts,72 (22 females, 50 males) are evaluable for response and toxicity.Median age was 55.6 years (28-80), and median Karnofsky performancestatus was 80% (70–100). Sites of measurable disease wereinoperable primary tumors/local recurrence (18), liver metastasis(22), lymph nodes (31) and peritoneum (20). One pt had bonemarrow metastasis and another had paraneoplastic hyperfibrinolyticcoagulopathy. RESULTS: 10/72 pts had complete response, 20/72 pts par tial response,40/72 pts tumor stabilization and 2/72 pts progressive disease.The median duration of response (CR/PR) was 9 months, the medianprogression-free interval 6 months, the median survival timewas 9 months, and for responding patients (CR/PR) 12.5 months.Toxicity: 1/72 pts had WHO grade 4 toxicity (diarrhea), 5/72pts had WHO grade 3 toxicity (nausea 1, diarrhea 4). Exceptfor 1 treatment-limiting grade 4 toxicity, no modificationsof dose or schedule due to toxicity were required. Thirty-sixof 44 pts experienced a significant reduction in tumor-relatedpain under treatment. CONCLUSION: Biochemical modulation of FU with FA and IFN is effective inadvanced gastric cancer. Moderate toxicity, outpatient treatmentsetting and high rates of amelioration tumor-related pain contributeto an effective palliation. advanced gastric cancer, double modulation of FU, phase II trial     

Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial

PURPOSE:: To compare mitomycin C plus vindesine plus etoposide (MEV) vs.mitomycin C plus vindesine plus cisplatin (MVP) in the treatmentof stage IV non-small-cell lung cancer. PATIENTS AND METHODS:: 204 patients were entered in a phase III multicentre randomisedtrial from June 1990 to December 1994 and stratified accordingto the ECOG performance status (0–1 vs. 2). MVP was givenin the following dosages: mitomycin C 8 mg/m² + vindesine 3mg/m² + cisplatin 100 mg/m² i.v. day 1 and vindesine 3 mg/m²i.v. day 8 with cycles repeated every 4 weeks. MEV was givenin the following dosages: mitomycin C 8 mg/m² + vindesine 3mg/m² i.v. day 1 and etoposide 100 mg/m² i.v. days 1 to 3 withcycles repeated every 3 weeks. For both treatments a maximumof 6 cycles was planned. Response and toxicity were evaluatedaccording to WHO. Subjective responses were assessed by numericalscales. Analyses were made on the basis of intent to treat. RESULTS:: The objective response rate was 21.4% (1 CR + 21 PR among 103patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients)in the MVP arm (P=0.48). Symptoms were similar in the two arms.196 patients progressed and 182 died. The median times to progressionwere 10 weeks (95% CI 9–12) and 12 weeks (95% CI 10–15)and median survivals were 29 weeks (95% CI 25–36) and28 weeks (95% CI 25–35) in the MEV and MVP arms, respectively.The relative risks of progressing and of dying were 0.89 (95%CL 0.66–1.20) and 0.96 CL 0.71–1.30), respectively,for patients receiving MVP as compared with those receivingMEV at multivariate analysis adjusted by sex, age, histologictype, number of metastatic sites, performance status at entry,and centre. CONCLUSIONS:: In the present study, no significant dfferences were observedin response rate, survival or palliation of symptoms betweenthe MEV and MVP regimens, while toxicity was significantly morefrequent and severe with MVP. Thus, MEV should be considereda reasonable alternative to the MVP regimen in the treatmentof stage IV NSCLC. chemotherapy, non-cisplatin-containing, regimen, stage IV NSCLC     

Intensive Chemotherapy with Cisplatin,Mitoxantrone, Methotrexate and Vincristine in Metastatic Breast Cancer

Summary

Eleven patients (pts) with advanced refractory breast carcinoma were treated with combination chemotherapy (Planovin) including mitoxantrone 10 mg/m² on day 1, cisplatin 60 mg/m² on days 1-2, methotrexate 200 mg/m² on day 15, vincristine 2 mg on day 15, leucovorin 15 mg/m² on days 15-16 every 3 weeks. Five patients (41%) achieved an objective response with one complete regression. The median duration of response was 4.5 months and the median duration of survival was 8 months. Drug related toxicity consisted mainly of leukopenia (8 pts), nausea and vomiting (6 pts), anemia (7 pts) and thrombocytopenia (4 pts).     

A phase II trial of dacarbazine, fluorouracil and epirubicin in patients with neuroendocrine tumours. A study by the Italian Trials in Medical Oncology (I.T.M.O.) Group

BACKGROUND: Previous experiences in the treatment of neuroendocrine tumourshave demonstrated some activity of single agents such as adriamycin,fluorouracil (FU), streptozotocin and dacarbazine (DTIC). Opinionsconcerning the usefulness of polychemotherapy in carcinoid tumoursare discordant, whereas better results have been achieved inother endocrine pancreatic neoplasms. Based on this background,we used multidrug chemotherapy with DTIC, FU and epirubicinin the treatment of different neuroendocrine tumours. METHODS: The study involved 38 pts with progressive and measurable disease.The treatment schedule was FU 250 mg/m² i.v., epirubicin 25mg/m² i.v., and DTIC 200 mg/m² i.v. on days 1, 2 and 3 every3 weeks. RESULTS: The responses achieved by histologic types were carcinoids 2/20,medullary thyroid carcinoma 1/7, neuroendocrine tumours 1/6;and Merkel cell carcinoma 3/5. The median duration of responsewas 5 months (range 2–11). Stable disease was observedin 13 cases (34%). Out of the 18 cases in progression, 17 hadnot responded to previous medical treatment. No symptom controlwas observed in 4 pts with carcinoid syndrome. Treatment toxicitywas moderate and included nausea and vomiting, alopecia, leukopeniaand mucositis. CONCLUSIONS: Our results document the moderate efficacy of the regimen inall of the histologic types. The major difference in comparisonwith previous studies was the lower response rate observed inpatients with neuroendocrine tumours. dacarbazine, epirubicin and fluorouracil combination, neuroendocrine tumours, carcinoids     

A Phase I Trial of 5-Fluorouracil with Cisplatin and Concurrent Standard-dose Radiotherapy in Japanese Patients with Stage II/III Esophageal Cancer

Objective: In Japan, 5-fluorouracil (5-FU) 400 mg/m² on Days 1–5,8–12, 36–40 and 43–46 with cisplatin (CDDP)40 mg/m² on Days 1, 8, 36 and 43 plus concurrent radiotherapywith 2 weeks planned interruption (60 Gy) was standard for thepatients with esophageal cancer. This Phase I trial was designedto determine the maximal tolerated dose (MTD) and dose-limitingtoxicity (DLT) of 5-FU on Days 1–4 and 29–32 withCDDP on Days 1 and 29 plus concurrent radiotherapy (50.4 Gy)among the Japanese. Methods: Escalating doses of 5-FU and CDDP were administered with concurrentradiotherapy (50.4 Gy). Treatment was continued until DLT appeared. Results: Twelve patients with previously untreated clinical Stage II/IIIsquamous cell esophageal carcinoma were studied. One of sixpatients given Level 1 (5-FU 800 mg/m² on Days 1–4 and29–32 with CDDP 75 mg/m² on Days 1 and 29) developed aDLT of incomplete protocol treatment due to Grade 3 esophagitis.The MTD was not reached at Level 2 (5-FU 1000 mg/m² with CDDP75 mg/m²). The complete response rate was 67% at Level 1 and100% at Level 2. Conclusions: Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanesepatients.     

High-dose carboplatin,thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma

Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0–M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m²/day) on days −8 to −6, and thiotepa (300 mg/m²/day) and etoposide (250 mg/m²/day) on days −5 to −3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6–44.7 years (median 13.8 years) at ASCR, were treated. Three (12%) died of treatment-related toxicities within 30 days of ASCR, due to multiorgan system failure (n = 2) and aspergillus infection with veno-occlusive disease (n = 1). Tumor recurred in 16 at a median of 8.5 months (range 2.3–58.5 months). Six are event-free survivors at a median of 151.2 months post-ASCR (range 127.2–201.6 months). The Kaplan–Meier estimate of median overall survival is 26.8 months (95% CI: 11.9–51.1 months) and of event-free survival (EFS) and overall survival are both 24% (95% CI: 9.8%–41.7%) at 10 years post-ASCR. M-0 (vs M-1 + ) recurrence prior to protocol, lack of tissue confirmation of relapse, and initial therapy of radiation therapy (RT) alone (vs RT + chemotherapy) were not significantly associated with better EFS (P = .33, .34, and .27, respectively). Trends toward better EFS were noted in patients (n = 5) who received additional RT as part of their retrieval therapy (P = .07) and whose recurrent disease was demonstrated to be sensitive to reinduction chemotherapy (P = .09). This retrieval strategy provides long-term EFS for some patients with previously irradiated recurrent medulloblastoma. The use of additional RT may be associated with better outcome.