Treatment of indolent B-Cell nonfollicular lymphomas: final results of the LL01 randomized trial of the Gruppo Italiano per lo Studio dei Linfomi.

PURPOSE: To evaluate the effect of epirubicin on therapeutic response and survival in patients with indolent nonfollicular B-cell lymphomas (INFL) treated with pulsed high-dose chlorambucil. PATIENTS AND METHODS: A total of 170 untreated patients with advanced/active INFL were randomly assigned to receive either eight cycles of high-dose chlorambucil (15 mg/m2/d) plus prednisone (100 mg/d) for 5 days (HD-CHL-P; arm A) or eight cycles of HD-CHL-P plus epirubicin 60 mg/m2 intravenous on day 1 (arm B). The responding patients were randomly assigned to either maintenance therapy with interferon alfa (IFNalpha-2a; 3 MU, three times weekly) for 12 months or observation. RESULTS: There were 160 assessable patients (82 males, 78 females; median age, 63 years; range, 33 to 77 years); 77 patients were assigned to arm A, and 83 were assigned to arm B. Induction therapy led to 47 complete responses (CRs; 29.4%) and 68 partial responses (PRs; 42.5%), with no significant difference between the two arms (60 CR + PR in arm A [77.9%] and 55 CR + PR in arm B [66.3%]; P =.07). After a median follow-up of 38 months (range, 2 to 103 months), there was no between-group difference in overall survival (OS; P =.45), failure-free survival (P =.07), or progression-free survival (PFS; P =.5). Eighty-eight patients were randomly assigned to either IFNalpha-2a (n = 43) or observation (n = 45), without any difference in 3-year PFS (44% and 42%, respectively). Univariate analysis showed that OS was influenced by age, anemia, serum lactate dehydrogenase levels, and International Prognostic Index distribution; multivariate analysis identified age and anemia as having influence on OS. CONCLUSION: HD-CHL-P treatment outcome in INFL patients was good (50% 3-year PFS, minimal toxicity, and low costs); epirubicin did not add any advantage. One-year IFNalpha maintenance treatment did not prolong response duration.     

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.     

Bleomycin,epidoxorubicin, cyclophosphamide,vincristine and prednisone (BACOP) in patients with follicular non-Hodgkin's lymphoma: results of a prospective,multicenter study of the Gruppo Italiano Per Lo Studio Dei Linfomi (GISL)

At present we report the results of a prospective, non-randomized open trial, conducted on follicular lymphoma (FL) patients by the Gruppo Italiano per lo Studio dei Linfomi (GISL), after a median follow-up of 62.6 months. Seventy-three patients with FL were registered to the study and treated with combination chemotherapy consisting of cyclophosphamide, epidoxorubicin, vincristine, bleomycin and prednisone, weekly administered every 4 weeks. After chemotherapy, involved-field radiotherapy was delivered in case of either localized, bulky and extranodal disease at presentation or limited residual disease at the end of chemotherapy. Patient received four or eight chemotherapy courses in case of localized or advanced disease, respectively. The overall response rate at the end of the treatment program was 97.3%, with 78.1% CR and 19.2% PR. CR rate was 94.3 and 63.1% in stage I-II and III-IV, respectively ( p =0.006). Beside the stage, response rate was significantly influenced by bone marrow involvement, and the number of extranodal sites. Relapse free survival was 60.8% at 5 years in the whole series; in localized disease it was 70.3 vs. 44.8% in advanced disease ( p =0.044) . Relapse free survival was significantly influenced by stage, bone marrow involvement, number of extranodal sites and International Prognostic Index (IPI) score. The overall 5-year survival rate was 90.2%; being 95.6% for patients with stage I-II and 85.1% for those III-IV ( p =0,0133). In addition, both IPI and Italian Lymphoma Intergroup (ILI) score had a significant impact on survival. The toxicity profile of the treatment was acceptable. From the results of this prospective study it is possible to conclude that this regimen and the whole treatment program is effective as first line therapy for the general population of FL. In particular the BACOP schedule is a valid anthracycline-containing regimen, and in this respect suitable to be considered as a treatment option.     

Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma: the experience of the Gruppo Italiano Studio Linfomi

BACKGROUND: The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS: One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EF-RT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp schedule, intervals between cycles were 21 days instead of 28 days, bleomycin doses were reduced, small doses of prednisone were given orally, and the interval before RT was prolonged. RESULTS: Clinical response was complete in 96% of patients who were treated with VBM plus EF-RT and in 94% of patients who were treated with VbMp plus IF-RT. Recurrence rates were nearly identical (12% and 11%, respectively) over necessarily different follow-up (91 months and 33 months, respectively). Hematologic toxicity was tolerable in both trials, and pulmonary side effects were moderate in the first trial and negligible in the second. On the whole, treatment was tolerated better when RT followed chemotherapy. CONCLUSIONS: The VBM regimen was confirmed to be effective in patients with early-stage Hodgkin lymphoma. Administration of all cycles before RT improved tolerance; pulmonary toxicity probably is mitigated further by reduced bleomycin doses, mild prednisone therapy, and a more prolonged resting interval before RT. A slightly higher recurrence rate was expectable in the VBM plus IF-RT trial despite the actual intensification of vinblastine and methotrexate.     

Long term results of a randomized study performed by Intergruppo Italiano Linfomi comparing Mini-CEOP vs P-VEBEC in elderly patients with diffuse large B-cell lymphoma

The Intergruppo Italiano Linfomi started, in 1996, a randomized trial for the initial treatment of elderly patients (older than 65 years) with Diffuse Large B-Cell Lymphoma (B-DLCL) comparing 6 courses of Mini-CEOP vs 8 weeks of P-VEBEC chemotherapy. Study objectives were survival, response and Quality of Life (QoL). Two hundred and thirty-two patients were evaluable for final analysis. Complete Response (CR) and Overall Response Rates (ORR) were 54% vs 66% (p = 0.107) and 90% vs 78% (p = 0.021) for P-VEBEC and Mini-CEOP, respectively. With a median follow-up of 72 months, the 5-year Overall Survival (OS), Relapse Free Survival (RFS), and Failure Free Survival (FFS) were 32%, 52%, and 21%, respectively. Subjects achieving a CR showed improvement of QoL regardless of treatment arm. Both Mini-CEOP and P-VEBEC determined a similar outcome for elderly patients with B-DLCL, with a third of patients alive after more than 6 years of follow-up. Both regimens can be considered equally for combination treatment with anti-CD20 monoclonal antibody.     

Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

BACKGROUND: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. PATIENTS AND METHODS: Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. RESULTS: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). CONCLUSIONS: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.     

Second-line chemotherapy with irinotecan plus carmustine in glioblastoma recurrent or progressive after first-line temozolomide chemotherapy: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

PURPOSE: Glioblastoma multiforme (GBM), the most frequent brain tumor in adults, is not considered chemosensitive. Nevertheless, there is widespread use of first-line chemotherapy, often with temozolomide, as a therapeutic option in patients with progressive disease after surgery and radiotherapy. However, at the time of second recurrence and/or progression, active and noncross-resistant chemotherapy regimens are required. The aim of the present multicenter phase II trial, therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and irinotecan chemotherapy. PATIENTS AND METHODS: Patients with histologically confirmed GBM, recurring or progressing after surgery, standard radiotherapy and a first-line temozolomide-based chemotherapy, were considered eligible. The primary end-point was progression-free survival at 6 months (PFS-6), and secondary end-points included response rate, toxicity, and survival. All patients were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6 weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the irinotecan dose was increased to 200 mg/m2. RESULTS: A total of 42 patients (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to 90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable. CONCLUSION: The BCNU plus irinotecan regimen seems active and non-cross-resistant in patients with GBM with recurrence after temozolomide-based chemotherapy.     

Vinorelbine, gemcitabine, procarbazine and prednisone (ViGePP) as salvage therapy in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL): results of a phase II study conducted by the Gruppo Italiano per lo Studio dei Linfomi

Patients with aggressive NHL who fail initial treatment or subsequently relapse have a very poor outcome and less than 20-25% achieve a prolonged disease-free interval with salvage therapies. To improve the outcome of patients with refractory aggressive NHL not suitable for High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT), the efficacy of a combination of gemcitabine, vinorelbine, procarbazine and prednisone (ViGePP) were tested. Between November 1999 and September 2002, 69 patients with relapsed or refractory aggressive NHL were treated with ViGePP regimen, every 4 weeks up to six courses. At the end of planned chemotherapy patients could receive additional radiotherapy on residual masses or on sites of previously bulky disease. Sixty-six patients were available for evaluation of study end-points. Thirty patients were refractory to therapy and 36 patients had relapsed after remission obtained with previous therapy. At the end of therapy, complete remission (CR) rate was 23%, 3-year relapse free survival rate was 40% and 3-year overall survival rate was 25% for the whole series (29% and 20% for relapsed and refractory patients, respectively). Patients achieving CR with ViGePP had a significantly better survival as compared with the remaining ones (p = 0.0003). ViGePP as used in the present setting has demonstrated a promising activity, comparable to other conventional dose regimens. Although CR was achieved only in a minority of patients, this was durable in a significant proportion of them. This regimen should be tested in less heavily pre-treated patients and probably in combination with new active agents such Rituximab. Further developments of this combination are warranted.     

The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases

In order to elucidate the role of anthracycline based combination chemotherapy regimens for the treatment of follicular lymphoma we conducted a retrospective study on a large series of patients with a histologically confirmed diagnosis of follicular lymphoma. The Italian lymphoma intergroup (ILI) promoted a retrospective study of patients with follicular lymphoma treated in cooperative trials between 1985 and 1996. Six hundred and thirty three cases were treated with an anthracycline-containing regimen and 128 patients were treated without anthracyclines. The two groups were prognostically comparable; in particular, no difference was observed according to both IPI and ILI prognostic index. Results showed a complete remission (CR) rate for patients treated with anthracyclines was 69.2% and overall response rate was 92.5%. After a median follow-up of 51 months (54 months for patients still alive), the 5- and 10-year overall survival (OS) rates were 80 and 66%, respectively. Disease-free survival (DFS) and failure-free survival (FFS) rates at 5 years were 61 and 49%, respectively. In the group of patients treated with combination chemotherapy not including anthracyclines, the CR rate was 67.5% and the overall response rate was 85.4%. A longer OS (80% at 5 years) was observed in patients treated with anthracyclines compared to 67% OS rate in patients treated without anthracyclines (p = 0.0004). FFS was significantly longer in patients treated with anthracyclines (49 vs. 34% p = 0.006). Patients treated with anthracyclines with low or intermediate risk according to ILI prognostic index showed a significantly longer OS (p = 0.0001 andp = 0.0009, respectively); those in the high-risk group showed a trend for a longer survival. In conclusion, this retrospective study shows that patients with follicular lymphoma treated with an anthracycline containing regimen had a better outcome compared to patients treated with other combination regimens non including anthracyclines in terms of CRs, OS and FFS. On the basis of these results anthracycline-containing regimens (ACR) should be considered as the standard treatment of patients with advanced follicular lymphoma.     

Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study).

BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.     

A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.     

Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi

BackgroundTumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL).Patients and methodsWe carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control.ResultsFor entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%–82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%–53%). In multivariate analysis, the use of AT during the patients’ life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%–73%). CR + PR rate was 85% with AT as second-line treatment.ConclusionAT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.     

Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.     

Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma

BackgroundPixantrone is an aza-anthracenedione with enhanced, preclinical antitumor activity and reduced cardiotoxicity compared with doxorubicin.Patients and methodsWe compared the efficacy and toxic effect of CPOP-R (substituting pixantrone for doxorubicin) against CHOP-R in untreated, diffuse large B-cell lymphoma (DLBCL) patients. The primary objective was to demonstrate non-inferiority of CPOP-R by complete response/complete response unconfirmed (CR/CRu) rate.ResultsThe CR/CRu rate for CPOP-R was 75% versus 84% for CHOP-R. Three-year overall survival was lower for CPOP-R (69% versus 85%) (P = 0.029). Median progression-free survival (PFS) was not reached for CPOP-R and was 40 months for CHOP-R [HR 95% confidence interval (CI) = 1.02 (0.60, 1.76), P = 0.934]. Fewer CPOP-R patients developed congestive heart failure (CHF) (0% versus 6%, P = 0.120), ≥20% declines in ejection fraction (2% versus 17%, P = 0.004), or elevations in troponin-T (P = 0.003).ConclusionsCPOP-R is an active regimen with modestly lower response rates than CHOP-R but similar PFS and event-free survival. This study demonstrates a substantially lower cardiotoxicity of pixantrone compared with doxorubicin when used as first-line therapy in DLBCL.     

Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: A meta-analysis of published randomised trials: A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente)

Background: Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastriccancer failing to show a clear indication; previous meta-analysessuggested small survival benefit of adjuvant chemotherapy, butthe statistical methods used were open to criticisms. Materials and methods: Randomised trials were identified bymeans of Medline and CancerLit and by selecting references fromrelevant articles. Systematic review of all randomised clinicaltrials of adjuvant chemotherapy for gastric cancer comparedwith surgery alone, published before January 2000, were considered.Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratioand its 95% confidence intervals (95% CI), derived accordingto the method of Parmar, were the statistics chosen for summarisingthe relative benefit of chemotherapy versus control. Results: Overall 20 articles (21 comparisons) were consideredfor analysis. Three studies used single agent chemotherapy,seven combination of 5-fluorouracil (5-FU) with anthracyclin,ten combination of 5-FU without anthracyclines. Informationon 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio0.82, 95% CI: 0.75–0.89, P < 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significantimprovement when compared with the effect of the other regimens. Conclusions: Chemotherapy produces a small survival benefitin patients with curatively resected gastric cancer. However,taking into account the limitations of literature based meta-analyses,adjuvant chemotherapy is still to be considered as an investigationalapproach. adjuvant, chemotherapy, gastric cancer, meta-analysis, randomised clinical trial     

Clinical relevance of immunophenotype in a retrospective comparative study of 297 peripheral T-cell lymphomas, unspecified, and 496 diffuse large B-cell lymphomas: experience of the Intergruppo Italiano Linformi

BACKGROUND: To assess the impact of T-cell/B-cell phenotype on clinical outcome, the authors retrospectively compared patients who had peripheral T-cell lymphoma, unspecified (PTCL-U), with patients who had diffuse large B-cell lymphoma (DLBCL). METHODS: Two hundred ninety-seven cases of PTCL-U and 496 cases of DLBCL that had been transferred from the files of the Intergruppo Italiano Linfomi or the Gruppo Italiano Linfomi were integrated into a unique working file and reviewed by the authors. RESULTS: The PTCL-U group and the DLBCL group had significantly different distribution patterns with respect to patient age, gender, disease stage, performance status (PS), the presence or absence of systemic "B" symptoms, the presence or absence of bulky disease, lactic acid dehydrogenase (LDH) levels, and number of extranodal sites (ENS). A significantly greater number of patients in the DLBCL group experienced complete remission (P < 0.0001). Multinomial logistic regression analysis confirmed that immunophenotype, PS, LDH concentration, and number of ENS were independent predictors of response. At a median follow-up duration of 43 months, there was no observable difference in disease-free survival (DFS) between patients with DLBCL and patients with PTCL-U; however, multivariate analysis did reveal that poorer PS and bone marrow involvement were significantly associated with shorter DFS. Furthermore, although the overall survival (OS) curves associated with the T-cell and B-cell immunophenotypes were significantly different from each other at a median follow-up duration of 37 months (P = 0.0012), Cox multivariate analysis excluded immunophenotype from the final OS model. CONCLUSIONS: The findings made in the current study indicate that the natural history of PTCL-U may differ from that of DLBCL. Patients with PTCL-U tended to have less favorable clinical outcomes, although the observed difference in outcome was only partially attributable to immunophenotype, which was independently associated with response, but not with survival. Differences in prognostic factor distributions between patients with PTCL-U and patients with DLBCL may account for some portion of the expected phenotype-associated risk.     

ProMECE-CytaBOM vs MACOP-B in Advanced Aggressive Non-Hodgkin's Lymphoma: Long Term Results of a Multicenter Study of the Italian Lymphoma Study Group (GISL)

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m² of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure.

Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11). We observed an eventual total of 120 treatment failures, 64 (61%) in the group treated with P-C and 56 (54%) among those treated with M-B (P = 0.29). Patients alive without disease at four years were estimated to be 42% in the P-C arm and 49% in the M-B arm (P = 0.27). The estimated 4-year overall survival was 54% for P-C and 61 % for M-B, and the differences were also not significant (P = 0.29). Patients treated with M-B experienced more and more severe side effects, including mucositis, infections, neurologic, pulmonary and cardiac abnormalities. Patients treated with P-C had a 1.3 g mean decrease of hemoglobin over the induction therapy, while patients treated with M-B experienced a 2.2 g mean decrease (P = 0.01).

In conclusion, both P-C and M-B resulted in effective treatment for patients with aggressive NHL, and provided similar activity. However P-C was more manageable in an outpatient setting and produced less acute toxic effects.     

Efficacy of carboplatin with an MEP (mitoxantrone, etoposide and prednisone) regimen for relapsed and CHOP-resistant diffuse large B-cell lymphomas.

Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.     

Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d'Etude des Lymphomes Agressives).

The prognostic significance of phenotype in malignant lymphomas (ML) is a matter of controversy. Here we analyze the clinical presentation, response to treatment, and survival of the 361 phenotyped patients with ML who were treated by the LNH-84 regimen. Histologic subtypes were diffuse-small cell in 10 patients, diffuse mixed in 69, diffuse large-cell in 177, immunoblastic in 94, and anaplastic large-cell in 11. One hundred and eight patients (30%) had a peripheral T-cell ML and 253 (70%) a B-cell ML. Most of B-cell MLs were of diffuse large-cell type, and the T-cell MLs were distributed among diffuse mixed and immunoblastic subtypes. T-cell MLs had an aggressive presentation with more patients having advanced stage (21% versus 41% stage II, 53% versus 45% stage IV, p = .0002), and B symptoms (58% versus 42%, p less than .01). The only significant difference in clinical manifestations were the higher frequency of gastrointestinal involvement in B-cell MLs (20% versus 2%, p less than .0001) and the more frequent spleen (39% versus 21%, p = .0005) and skin (19% versus 3%, p less than .0001) involvement in T-cell MLs. There was no difference in response to the LNH-84 regiment between the two subgroups, but T-cell ML patients relapsed at a higher rate (43% versus 29%, p less than .001). T-cell ML patients have a significantly shorter freedom-from-relapse (FFR) survival (median: 34 months versus not reached, logrank test: p = .002) and a non-significant shorter overall survival (median: 42 versus 50 months).(ABSTRACT TRUNCATED AT 250 WORDS)