Umberto Tirelli

CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group.

PURPOSEnWe report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy regimen specifically devised for elderly patients, ie, etoposide, mitoxantrone, and prednimustine (VMP), versus the standard regimen of cyclophosphamide, doxorobucin, vincristine, and prednisone (CHOP) in patients older than 70 years of age with intermediate- and high-grade non-Hodgkins lymphoma (NHL).nnnPATIENTS AND METHODSnPatients older than 70 years of age with stage II, III, or IV intermediate- and high-grade NHL, with an Eastern Cooperative Oncology Group (ECOG) performance status less than 4 and acceptable cardiac, renal, and liver function were randomized to receive six courses of VMP or six courses of CHOP. Between February 1989 and June 1994, 130 patients aged 70 to 93 years (median, 75) were enrolled and 120 were assessable for response, 60 patients in each arm.nnnRESULTSnOverall objective response rates were 50% and 77% in VMP- and CHOP-treated patients, respectively (P = .01), while complete response (CR) rates were borderline significant (27% v 45%; P = .06). At 2 years, the progression-free survival (PFS) rate was 25% with VMP versus 55% with CHOP (P = .002) and the overall survival (OS) rate was 30% with VMP versus 65% with CHOP (P = .004). Statistically significant more alopecia and neurologic and gastrointestinal toxicities were reported with CHOP.nnnCONCLUSIONnCHOP is the standard regimen for patients > or = 70 years of age with stage II to IV intermediate- and high-grade NHL.

Combined-Modality Therapy for Clinical Stage I or II Hodgkin's Lymphoma: Long-Term Results of the European Organisation for Research and Treatment of Cancer H7 Randomized Controlled Trials

PURPOSEnIn early-stage Hodgkins lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control.nnnPATIENTS AND METHODSnPatients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT.nnnRESULTSnMedian follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175).nnnCONCLUSIONnA treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Quality of life after successful treatment of early-stage Hodgkin's lymphoma: 10-year follow-up of the EORTC–GELA H8 randomised controlled trial

BACKGROUNDnLittle is known about the longitudinal course of health-related quality of life (HRQoL) in patients with Hodgkins lymphoma during their post-treatment follow-up and re-adaptation to normal life. We report on the HRQoL of patients treated in the randomised H8 trial of the European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group and the Groupe dEtudes des Lymphomes de lAdulte (GELA). We aimed to assess HRQoL and fatigue following treatment, to analyse relations with treatment, and to identify factors that predict persistent fatigue.nnnMETHODSnPatients received HRQoL questionnaires at the end of primary therapy and during follow-up. The EORTC QLQ-C30 was used to assess HRQoL, and the Multidimensional Fatigue Inventory (MFI-20) was used to assess fatigue. Changes of mean HRQoL scores over time were analysed with mixed models. Multiple polytomic nominal logistic regression was done to identify independent baseline predictors of fatigue within MFI-20 dimensions. Analyses were done on an intention-to-treat basis. This study is registered with www.ClinicalTrials.gov, number NCT00379041.nnnFINDINGSn2666 assessments from 935 patients were analysed. Mean follow-up was 90 months (range 52-118). Age affected all functioning and symptom scores except emotional functioning, with younger age associated with higher functioning and lower severity of symptoms; improvement with time showed similar patterns between age groups. Women reported lower HRQoL and higher symptom scores than did men. Overall, 3.2% (14/439 for role functioning) to 9.7% (43/442 for social functioning) and 5.8% (29/498 for reduced motivation) to 9.9% (49/498 for general fatigue) of patients reported impairments of 10 points or more (on a 0-100 scale) in QLQ-C30 and MFI-20 scores, respectively, independent of age and sex. Emotional domains were more affected than physical ones. There was no relation between HRQoL outcome and type of treatment. Fatigue (MFI-20 scores) at the end of treatment was the only predictive variable for persistent fatigue, with odds ratios varying from 2.58 (95% CI 1.00-6.67) to 41.51 (12.02-143.33; p</=0.0001). Sensitivity analyses adjusting for missing data were much the same as the main results.nnnINTERPRETATIONnHRQoL data after treatment for early-stage Hodgkins lymphoma show that patients experience strain and limitations in all subdomains apart from cognitive functioning (QLQ-C30), and also have reduced motivation (MFI-20). Differences in HRQoL improvement with time were linked to age and sex, but not type of treatment. Fatigue status at the end of treatment seems to predict subsequent HRQoL.nnnFUNDINGnFrench Ministry of Health, Programme Hospitalier de Recherche Clinique 1994, and French National League Against Cancer.

Phase II study of cytarabine in Hodgkin's disease

Abstract Cytarabine was administered to 24 patients with previously treated Hodgkins disease in the EORTC Lymphoma Cooperative Group. The drug was administered at the dose of 80 mg/m 2 subcutaneously twice a day on 5 consecutive days every 3 weeks. The overall response rate was 17.6% (3 responses among 17 evaluable patients) with a short duration (2–6 months). The main toxicity was myelosuppression. Our experience in the EORTC Lymphoma Cooperative Group could not demonstrate a significant activity at this dose and schedule in Hodgkins disease.

Comparison of 36 Gy, 20 Gy, or No Radiation Therapy After 6 Cycles of EBVP Chemotherapy and Complete Remission in Early-Stage Hodgkin Lymphoma Without Risk Factors : Results of the EORT-GELA H9-F Intergroup Randomized Trial

PURPOSEnWhile patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy.nnnMETHODS AND MATERIALSnPatients with untreated supradiaphragmatic HL without risk factors (agexa0≥xa050xa0years, 4 to 5 nodal areas involved, mediastinum-thoracic ratioxa0≥xa00.35, and erythrocyte sedimentation ratexa0≥xa050xa0mm in first hour without B symptoms or erythrocyte sedimentation ratexa0≥xa030xa0mm in first hour with B symptoms) were eligible for the trial.xa0Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20xa0Gy in 10 fractions), or standard-dose involved-field RT (36xa0Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36xa0Gy (n=239), 20xa0Gy of involved-field RT (n=209), or no RT (n=130).nnnRESULTSnRandomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%.nnnCONCLUSIONSnIn adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20xa0Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome.