P-VEBEC: A new 8-weekly schedule with or without rG-CSF for elderly patients with aggressive non-Hodgkin's lymphoma (NHL)

BACKGROUND: Chemotherapy regimens devised for elderly patients with intermediate-highgrade NHL are a matter of discussion. The aim is to reduce generaltoxicity without loosing an antilymphoma effect. The most importantlimiting factor of chemotherapy is myelotoxicity; for this reasonthe use of growth factor may be useful in these patients. PATIENTS AND METHODS: From November '91 to November '92, 67 pts older than 65 yearswith intermediate-arid high-grade advanced-stage NHL were treatedwith the P-VEBEC regimen, an original scheme with epirubicin50 mg/m², cyclophosphamide 350 mg/m² and etoposide 100 mg/m²on weeks 1, 3, 5, 7; vinblastine 5 mg/m² and bleomycin 5 mg/m²on weeks 2, 4, 6, 8, prednisone 50 mg/m²/day p. os in the first2 weeks and thereafter every other day. Twenty-eight pts receivedr-GSF 5 (µg/kg/day throughout the treatment starting onday 2 of every week for 4 consecutive days. Their median agewas 71 years (65–80), 31 pts were male and 36 female,histology according W.F. was D 6; E 17; F 16; G 19; H 9. Twenty-fivepercent of pts had B symptoms, 35% had bulky disease, 41% LDHlevel > normal, 44% stage IV and 26% had B.M. involvement. RESULTS: CR. was achieved by 66% of pts. Adverse prognostic factors forCR were E histology, stage IV, bone marrow infiltration andLDH above normal. Severe toxicity was never recorded, no toxic death was observed.With a median follow-up of 24 months OS, DFS and EFS were 55%,52%, and 33%, respectively. EFS was influenced by stage, BMinvolvement and level of LDH. The relative dose intensity (RDI) was calculated by the methodof Hryniuk and Bush. Patients who received rG-CSF had a significantlyhigher median RDI (94% vs 79%) and lower myelotoxicity (neutrophilnadir <500 18% vs 56%). The rate of CR was influenced byRDI >80% (89% vs 56%). EFS was also better in pts who received a RDI higher than 80%(50% vs 18% p = 0.05). CONCLUSION: P-VEBEC is a feasible cycle in elderly patients; the use ofrG-CSF improves RDI. In patients with adverse prognostic factors(BM involvement, poor performance status) a RDI >0.80 couldplay a role in improving the outcome. lymphoma, elderly patients, rG-CSF     

Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer

Purpose: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. Methods: Previously untreated patients with small-cell lung cancer, with measurable disease, aged ≤ 72 years, performance status ≤ 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m² cisplatin on day 1, 100 mg/m² carboplatin on days 2, 3 and 8, and 50 mg/m² etoposide on days 1, 2, 3 and 8. Results: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. Conclusions: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer. Received: 21 May 1997 / Accepted: 11 September 1997     

Chemotherapy of malignant fibrous histiocytoma of bone

BACKGROUND:: Malignant fibrous histiocytoma of bone (MFHB) is a rare tumourwith a 3 year survival of 30%-40% when treated with surgeryalone. A small number of patients have previously been treatedwith pre-operative chemotherapy and responses observed. Theaim of the present study was to further determine the responseof MFHB to pre-operative chemotherapy. PATIENTS AND METHODS:: A non-randomised study of 18 patients with MFHB. Twelve hadlocalised disease and 6 had pulmonary metastases. In 14 patientspre-operative treatment consisted of methotrexate 8 g/m² onday 1, ifosfamide 3 g/m² and doxorubicin 60 mg/m² on day 10.This regimen was given twice and twice post-operatively. A further4 patients received cisplatin 100 mg/m² on day ] and doxorubicin25 mg/m² on days 1, 2, 3. Three cycles were given preand post-operatively. RESULTS:: 15 patients had surgery after chemotherapy. Tumour necrosiswas present in all resection specimens and ranged from 50%–100%.7/15 had >90% necrosis. Disease free survival is 82% forthose patients with a greater than 2 year follow-up. CONCLUSION:: This study confirms previous reports that MFHB is a chemosensitivetumour. In view of its rarity collaborative trials are neededto establish the optimum drug treatment including drug selectiondose and duration. bone sarcoma, chemotherapy     

Ifosfamide plus paclitaxel in advanced non-small-cell lung cancer: A phase I study

BACKGROUND:: ifosfamide and paclitaxel are active drugs in the managementof non-small-cell lung cancer. We have performed a phase I studyusing a fixed dose of ifosfamide with escalating doses of paclitaxel,with G-CSF support, in an effort to determine the maximum tolerateddose (MTD) of paclitaxel in this combination, and to describethe dose-limiting toxicities of the combination at the recommendedphase II dose of paclitaxel. We also studied the feasibilityof delivering the paclitaxel as a one-hour infusion at the recommended phase II dose. PATIENTS AND METHODS:: Thirty-one patients were treated, 25 with stage IV disease,and 6 with stage IIIB disease. Ifosfamide was administered ata dose of 1.6 g/m² i.v. bolus daily x 3 days, with mesna uroprotection.Paclitaxel was administered as a 24-hour infusion at dose levelsof 135, 170, 200, 250, and 300 mg/m² six patients were treatedwith a one-hour infusion, at a dose of 250 mg/m² G-CSF, 5 µ/kg,was administered subcutaneously on days 4 through 10, or untilthe absolute neutrophil count exceeded 4000/µl. Cycleswere repeated every 21 days. RESULTS:: The dose-limiting toxicity was granulocytopenia, which increasedwith increasing dose levels of paclitaxel. The MTD was 300 mg/m²of paclitaxel, and the recommended phase II dose 250 mg/m² administeredas a 24-hour infusion. Other toxicities were generally mild,with only 5 patients demonstrating grade 3 neurotoxicity and5 with grade 3 thrombocytopenia. Partial responses were seenin seven patients (23%), all in the 18 patients who receiveddose levels of 250 mg/m² or higher. CONCLUSIONS:: Ifosfamide plus paclitaxel is an active treatment regimen inadvanced non-small-cell lung cancer, and compares favorablywith the results of cisplatin-based chemotherapy. A phase IIstudy is in progress by the Cancer and Leukemia Group B, inan effort to better characterize the tolerance of the regimen,as well as its effect on tumor response and survival. non-small-cell lung cancer, chemotherapy, ifosfamide/paclitaxel     

The MINE regimen as intensive salvage chemotherapy for relapsed and refractory Hodgkin's disease

BACKGROUND: Relapsed or refractory Hodgkin's disease (HD) patients weretreated with an intensive salvage regimen (MINE) prior to high-dosetherapy (HDT) with hematopoietic stem cell support. PATIENTS AND METHODS: One hundred HD patients who either failed to respond to a front-linechemotherapy regimen (induction failure, n—41) or relapsed(untreated relapse, n—54; resistant relapse, n—5)were treated with the MINE regimen. Each course of MINE comprisedmitoguazone 500 mg/m² on days 1 and 5, ifosfamide 1500 mg/m²/dfrom day 1 to day 5, vinorelbine (Navelbine^®) 15 mg/m² ondays 1 and 5, and etoposide 150 mg/m²/d from day 1 to day 3.At least two courses were given at 4-week intervals. Then, 72patients received HDT followed by hematopoietic stem cell support. RESULTS: After MINE salvage, 34 patients achieved a complete response(CR) and 39 a partial response, yielding an overall responserate of 75%. Patients with untreated relapse had a 92.5% responserate and those with resistant relapse or induction failure a53% response rate. A total of 58 patients reached a CR at theend of all treatments; 12 of them relapsed. Sixty-six patientswere alive with a median follow-up of 26 months, including 46patients in CR. The 2-year survival rate for the entire groupwas 59%. By univariate analysis, patients with an interval betweentheir last treatment and salvage longer than 12 months, untreatedrelapse, or good performance status at salvage are shown tohave longer survivals. The main toxic effects were neutropenia,thrombo-cytopenia, and infectious episodes. Three patients diedof MINE-related complications and three after HDT. CONCLUSION: Given early in the course of progressive HD, the MINE regimenreduced tumor burden in a high proportion of patients with relapsedor refractory disease. Responding patients further intensifiedwith HDT have a better outcome than those who have not respondedto salvage treatment. Hodgkin's disease, salvage therapy     

Phase II study of intensive chemotherapy with carboplatin,ifosfamide and etoposide plus recombinant human granulocyte colony-stimulating factor and sequential radiotherapy in locally advanced,unresectable non-small-cell lung cancer

 From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m² on day 1, carboplatin given i.v. at 200 mg/m² on days 1 and 2, etoposide given i.v. at 120 mg/m² on days 1–3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 μg/kg on days 4–13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0–1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiothera-peutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III–IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses. Received: 26 November 1995/Accepted: 5 March 1996     

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.     

Concurrent Chemotherapy and Radiation Therapy for Locally Advanced Carcinoma of the Esophagus

A pilot study was undertaken to clarify the efficacy of concurrentchemoradiotherapy against locally advanced esophageal carcinoma.The 20 patients in this study had previously untreated esophagealcarcinoma with evidence of T4 disease and/or distant node metastases.Chemotherapy consisted of protracted infusion of 5-fluorouracilat a dose of 400 mg/m²/day on days 1–5 and 8–12,combined with a 2-h infusion of cisplatinum at 40 mg/m² on days1 and 8. Radiation treatment for the mediastinum was administered5 days per week for 3 wk at 2 Gy/day, along with chemotherapy.These schedules were repeated twice to give a total radiationdose of 60 Gy. For patients who responded, two additional coursesof chemotherapy were administered. Five of the 20 patients hadUICC stage III disease and 15 had stage IV. Seventeen (85%)of the 20 patients exhibited an objective response, including6 (30%) complete responses. Local control was excellent with10 (50%) complete responses. Toxic effects were severe. Majortoxicities were leukocytopenia of grade 3 or more in 45% ofthe patients and esophagitis, including four perforations. Therewere two treatment-related deaths. The median survival timewas 9 mo (range: 2 to 34+). Concurrent chemotherapy and radiotherapywas effective even for locally advanced esophageal carcinoma,but was associated with significant toxicity.     

Therapy studies of the German Hodgkin's Study Group. Intermediate results of the study protocols HD1, HD2, and HD3

Between July 1983 and September 1986 358 untreated patients with Hodgkin's lymphoma qualified for the protocols HD1 (stages I to IIIA with risk factors), HD2 (stage IIIA), and HD3 (stages IIIB and IVAB). Patients in HD1 received a combined chemo-radiotherapy (2 X COPP/ABVD + 40 Gy EF vs. 2 X COPP/ABVD + 20 Gy EF). Patients in HD2 were randomized into radiotherapy (TNI 40 Gy) vs. combined chemo-radiotherapy (2 X COPP/ABVD + 20 Gy IF). Patients in HD3 received induction chemotherapy (3 X COPP/ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 X COPP/ABVD). In HD1, 51 out of 65 evaluable patients (78%) achieved a complete remission. The survival of HD1 patients is as good as the survival of patients in stages I and II without risk factors. In HD3, 58 out of 93 patients (62%) achieved complete remission after induction chemotherapy with COPP/ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 71% complete remissions in stages IIIB/IVAB were achieved. The progression-free survival of HD3 patients who received consolidation therapy is significantly longer than of patients who refused consolidation therapy.     

Paclitaxel/cisplatin in advanced non-small-cell lung cancer (NSCLC)

Background: Paclitaxel (Taxol^®) as single agent has shownpromising activity in advanced non-small-cell lung cancer (NSCLC).Because paclitaxel lends itself to combination with other anticancerdrugs, we have determined the efficacy of paclitaxel combinedwith cisplatin in patients with advanced NSCLC in a phase IItrial Patients and methods: Twenty patients with NSCLC stage IIIBor IV were treated with paclitaxel (175 mg/m²) as a 3-hour infusionafter standard premedication on day 1 and cisplatin (50 mg/m²daily) on days 1 and 2. Treatment was repeated every 3 weeks Results: All 20 patients were evaluable for response and toxiceffects. Partial responses were seen in 7 (35%) patients andno change in 9 (45%) patients. Major side effects included leukopenia,anemia, alopecia and dose-limiting neurotoxicity chemotherapy, cisplatin, neurotoxicity, non-small-cell lung cancer, paclitaxel, phase II trial, Taxol^®     

Cisplatin-based chemotherapy and hyperfractionated radiotherapy for stage III non-small cell lung cancer: survival and patterns of failure after long follow-up

The main purpose of this prospective non randomized trial was to analyse whether induction chemotherapy and hyperfractionated radiotherapy combined with cisplatin can improve the long-term survival of patients with locally advanced non small cell lung cancer. From 1992 to 1995, 70 patients received the programmed treatment scheme with: one cycle of induction chemotherapy with mitomycin 10 mg/m²/day 1, cisplatin 100 mg/m² day 1 and vindesine 3 mg/m²/days 1, 8 and 15, followed after 4 weeks of hyperfractionated radiotherapy (1.2 Gy twice/day, five days per week, until total dose of 69.6 Gy) concomitant with cisplatin 20 mg/m²/day by continuous infusion, for 5 days in the first and fifth weeks of radiotherapy. Patients with stage IIIA, good performance status and radiological partial response were candidated to surgical rescue. Thirty-two patients (45.7%) developed severe toxicity (WHO grade 5–4). Complete radiological response was observed in 9 patients (12.8%). Overall median survival time was 14 months, 2-year survival of 20% and 5-year survival of 12%. The cause of dead was by local progression in 42%, distant metastases in 40%, simultaneous relapse in 10% and intercurrent disease in 8%. Patients with stage IIIA (n=16, 7 with surgical rescue) had a 5-year survival of 52%, and patients with stage IIIB (n=54) of 6%. Long-term results with this treatment scheme are disappointing, only patients with stage IIIA and surgical rescue showed an improvement on survival. In spite of chemotherapy and high radiation dose, local-regional progression and distant metastases remain significant patterns of failure and dead of these patients.     

Phase II study of sequential high-dose methotrexate (MTX) and 5-fluorouracil (F) alternated with epirubicin (E) and cisplatin (P) [FEMTX-P] in advanced gastric cancer

BACKGROUND:: FAMTX (5-fluorouracil, adriamycin, methotrexate) is one of themost effective drug combinations in gastric cancer. Therefore,modifications of FAMTX appear of interest and the FEMTX-P regimentwas conceived. PATIENTS AND METHODS:: Fifty patients with unresectable locally advanced and/or metastaticgastric carcinoma were treated with methotrexate 1500 mg/m²i.v. and 5-fluorouracil 1500 mg/m² i.v. on day 1; leucovorinrescue 15 mg/m² orally every 6 hours for 8 doses on days 2 and3; epirubicin 60 mg/ m² i.v. and cisplatin 50 mg/m² i.v. onday 15, q 4 weeks. RESULTS:: Of forty-seven patients evaluable for response, five (11%) achievedcomplete responses and seventeen (36%) partial responses (totalresponse rate 47%). The median duration of response was 8+ months(range: 5–25+ months). Four of 14 patients with locallyadvanced disease were successfully downstaged and subsequentlyresected. The median duration of survival of all patients was10 months (range: 1–25+ months). Leukopenia grade 4 occurredin 18% of patients and thrombocytopenia grade 4 and mucositisgrade 4 in 4% and 2%, respectively. Treatment postponement forhematologic toxicity was necessary in 54% of patients. CONCLUSIONS:: The FEMTX-P regimen is an active regimen in advanced gastriccarcinoma, with acceptable toxicity. chemotherapy, FEMTX-P, gastric cancer     

ChlVPP--an effective and well-tolerated alternative to MOPP therapy for Hodgkin's disease

The substitution of chlorambucil for nitrogen mustard and vinblastine for vincristine has been suggested to be an equally effective and well-tolerated variation of the MOPP regimen (mechlorethamine, vincristine, procarbazine, and prednisone). We treated 76 patients with advanced (i.e., Stage III, IV, or II with bulky mediastinal mass) or recurrent Hodgkin's disease with chlorambucil 6 mg/m2, procarbazine 100 mg/m2, and prednisone 40 mg p.o. daily, all on days 1-14; plus vinblastine 6 mg/m2 i.v. on day 1 and 8 of each 28-day cycle (ChlVPP). There was no maximum dose of the myelosuppressive agents. Patients who had not previously been irradiated received from 2,300 to 4,100 cGY to sites of previously bulky diseases after completing 6 cycles of ChlVPP. ChlVPP was easy to administer (i.e., 87% of patients without previous chemotherapy received greater than or equal to 80% of the planned doses of myelosuppressive drugs) and was generally well tolerated, with only occasional vomiting from procarbazine and phlebitis from vinblastine. In patients without previous chemotherapy, 49 (76%) achieved a complete remission (CR) and 7 (11%) a stable partial remission (i.e., residual, stable radiographic abnormality). With a maximum follow-up of 4 years, only one CR has relapsed for an actuarial CR durability of 97%. ChlVPP with consolidative radiation therapy to sites of bulky disease is effective in advanced Hodgkin's disease and, compared with most other available regimens, is extremely well tolerated.     

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     

5-Fluorouracil, hydroxyurea and escalating doses of iododeoxyuridine with concomitant radiotherapy for malignant gliomas: A clinical and pharmacologic analysis

BACKGROUND:: Iododeoxyuridine (IUdR) is a known radiation enhancer, and interactsbiochemically with 5-fluorouracil (5-FU) and hydroxyurea (HU) PATIENTS AND METHODS:: IUdR was added to the previously studied regimen of continuousinfusion 5-FU at 300 mg/ m²/day for 5 days, HU 500 mg every12 hours for 11 doses and radiotherapy 200 cGy/day for 5 days,all administered for 7 consecutive weeks to patients with malignantglioma. IUdR was administered as 5-day continuous intravenousinfusion during weeks 1 and 4. The IUdR dose was changed incohorts of patients. IUdR plasma concentrations were determinedduring weeks 1 and 4, and IUdR incorporation into the DNA ofgranulocytes was measured on weeks 2 and 5. RESULTS:: Two patients treated at the initial IUdR dose of 500 mg/m²/daydeveloped grade 3 or 4 myelosuppression and mucositis. Additionaldose levels of IUdR tested were 250 mg/m²/day and 125 mg/m²/day;at the latter dose, severe or life-threatening toxicity wasseen in only 3 of 8 patients treated. IUdR incorporation intoDNA of granulocytes was 10.5(± 2.3)% at an IUdR doseof 500 mg/mVday but decreased to 0.76(± 0.3)% at 125mg/m²/day. Similarly, lUdR plasma concentrations decreased from436 (± 114) ng/ml to 99(±29)ng/ml. CONCLUSIONS:: The addition of IUdR to 5-FU and HU results in significant systemictoxicity necessitating limitation of the IUdR dose to 125 mg/m²/day. There is a significant biochemical interaction betweenIUdR, 5-FU and HU leading to increased IUdR incorporation intoDNA and to substantial clinical toxicity. Further clinical studiesto exploit this interaction at more feasible schedules may beuseful. malignant gliomas, concomitant chemoradiotherapy, IUdR, fluorouracil, hydroxyurea     

ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score 相似文献   

A Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization

Background: We previously reported that arterial infusion chemotherapy improvedthe response rate and survival of the patients with pancreaticcancer at advanced stages in an open trial. We conducted a PhaseI trial of arterial infusion chemotherapy with gemcitabine and5-fluorouracil for advanced pancreatic cancer after vascularsupply distribution via superselective embolization. Methods: Patients were treated after arterial embolization for hemodynamicchange to restrict the blood flow into the pancreas (mainlyto the great pancreatic artery and the caudal pancreatic artery).Arterial infusion chemotherapy consisted of gemcitabine in dosesthat were increased from 600 to 1000 mg/m² in subsequent cohortson Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m²/dayon Days 1–5 every 2 weeks. Result: Twelve patients were enrolled. The maximum tolerated dose ofgemcitabine was determined to be Level 3 (1000 mg/m²). Onlyvery mild hematological and non-hematological toxicities werenoted. The overall response rate was 33.3%. The median survivaltime was 22.7 (95% CI; 9.5–24.5) months and the 1- and2-year overall survival rates were 83.3 and 25.0%, respectively. Conclusion: Arterial infusion chemotherapy using 1000 mg/m² gemcitabineon Day 1 and 300 mg/m²/day 5-fluorouracil on Days 1–5every 2 weeks warrants a Phase II study.     

Preoperative chemotherapy with cisplatin in combination with docetaxel and gemcitabine in locally advanced non-small-cell lung cancer

Despite surgery, both locoregional and distant disease controls remain poor in stage III non-small-cell lung cancer (NSCLC). Preoperative chemotherapy has become an accepted treatment but no established regimen exists. Our objective was to define the activity and feasibility of cisplatin in combination with docetaxel and gemcitabine in stage III NSCLC followed by surgery or radiotherapy. Thirty-two chemotherapy-naive patients with NSCLC (59% stage IIIAN2, 41% stage IIIB) received cisplatin 75 mg/m² on day 1, gemcitabine 1,000 mg/m² on days 1 and 8, and docetaxel 20 mg/m² on days 1, 8 and 15. Patients received induction chemotherapy (3 cycles) before re-evaluation, followed by thoracotomy or thoracic radiotherapy. Radiographic response was 50% and stable disease at computed tomography (CT) scan was observed in 30% of patients. Thirty patients were evaluable for response; thoracotomy was performed in 16 patients (53%) and resection was complete in 8 patients (27%). Grade 3/4 neutropenia, the main hematologic toxicity, occurred in 53% of patients but only 3 patients required hospitalization due to neutropenic fever. Severe non-hematologic toxicity was uncommon. There were 3 treatment-related deaths. To date, 22% of patients remain alive and disease-free with a median follow-up of 13 months. Median survival for all recruited patients was 14 months, with an estimated 1-year survival rate of 60%. The combination of cisplatin/docetaxel/gemcitabine is a welltolerated regimen. Although it has potential serious toxic effects, high response rates and manageable toxicity justify its use in further trials. The Spanish Lung Cancer Group (SLCG) is currently performing a trial with this regimen in stage III disease.     

Induction chemotherapy plus high-dose radiotherapy versus radiotherapy alone in locally advanced unresectable non-small-cell lung cancer

Background: High-dose radiation therapy is generally recommendedas standard treatment in regionally advanced unresectable non-small-celllung cancer (NSCLC), but medianand long-term survival remainpoor. Some reports have recently shown an improvement of resultsin advanced NSCLC when cisplatin was included in the chemotherapyregimens. Therefore, we designed a randomized trial to determinewhether induction chemotherapy before high-dose radiotherapyimproves response rate and survival in stage HI NSCLC over thatachieved with radiotherapy alone. Patients and methods: From March, 1984 to December, 1988, 66consecutive patients with stage HI unresectable NSCLC were randomizedto one of two treatment arms; 61 were evaluable for survivaland 58 for response and toxicity. Patients randomly assignedto arm A received cisplatin (CDDP 100 mg/m² on day 1) and etoposide(VP 16 120 mg/ m² on days 1, 2, 3) every 3 wks for 3 coursesfollowed by radiotherapy 56 Gy on pre-treatment tumor volumeand 40 Gy on mediastinum and bilateral supraclavicular nodes.Patients assigned to arm B received only the same radiotherapy.The 61 eligible patients were comparable in terms of age, performancestatus, histology and treatment. Results: Response rate was 53% in arm A and 32% in arm B. Themedian survival was 52 wks for the combined treatment arm and36 wks for the radiation therapy arm. At six years of follow-upall the patients were dead. Toxicity was mild and no treatment-relateddeaths were recorded. Conclusion: Induction chemotherapy produced a better responserate and a trend of improved survival (4 months) but a significantsurvival advantage was not achieved (p < 0.11), probablybecause of the small number of patients enrolled in the trial. chemotherapy, non-small-cell lung cancer, radiotherapy, combined treatment     

Therapy of Hodgkin's lymphomas. Results of the German Hodgkin's Disease Study Group

Between July 1983 and May 1987 143 untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors qualified for the HD1 protocol, and 230 patients in stages IIIB/IV qualified for HD3. Patients in HD1 received a combined chemo-radiotherapy (2 x COPP + ABVD + 20 Gy EF vs. 40 Gy EF). Patients in HD3 received induction chemotherapy (3 x COPP + ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 x COPP + ABVD). In HD1, 73 of 89 evaluable patients (82%) achieved a complete remission. The survival of patients in stages I-IIIA with risk factors treated according to HD1 is as good as the survival of patients in stages I and II without risk factors. In HD3, 86 of 137 patients (63%) achieved complete remission after induction chemotherapy with 3 x COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 x CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. An ESR greater than 80 mm/h was the most significant single risk factor in stages IIIB/IV for induction of CR and freedom from progression.