Intermediate stage Hodgkin lymphoma in partial remission after three or four courses of doxorubicin, bleomycin, vinblastine dacarbazine: no benefit of one course of intensive chemotherapy before irradiation.

The H97-I trial (1997-2004) for Hodgkin lymphoma at intermediate stage (HL-I) included 269 patients who were randomized to receive three or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The 197 patients who reached complete remission (CR) (73.2%, p = 0.41 between arms) received radiotherapy (RT); their 10-year progression-free survival (PFS) rate was 87.7 ± 3.0%, similar to that of the 180 patients of a historical control group (HCG) in CR after three ABVD cycles before RT. The 59 patients who reached post-ABVD partial remission (PR) received one course of intensive chemotherapy (i.v., mg/m(2), vindesine 5, adriamycin 90, BCNU 140, etoposide 600, methylprednisolone 600) before RT. In spite of this additional intensive chemotherapy, their PFS rate (78.4 ± 6.3%) remained significantly lower (p = 0.03) than that of the 197 patients who reached post-ABVD CR, and was similar to that of the 60 patients of the HCG in PR after three ABVD cycles who did not receive additional chemotherapy before RT.

Neoadjuvant dose-dense gemcitabine plus docetaxel and vinorelbine plus epirubicin for operable breast cancer: improved prognosis in triple-negative tumors.

BACKGROUND: Neoadjuvant anti-tumor activity of an alternating taxane- and anthracycline-based dose-dense regimen in patients with operable, non-inflammatory large breast cancer was investigated. OBJECTIVE: The objective is to study the rate of pathological complete response in patients with breast cancer receiving dose-dense chemotherapy sequentially with gemcitabine plus docetaxel and vinorelbine plus epirubicin. METHODS: Women (n = 74) with clinical stage II or III breast cancer were enrolled in this open-label, multicenter study to receive six 2-weekly courses of gemcitabine 1000 mg/m2 plus docetaxel 75 mg/m2 on days 1 and 15, and vinorelbine 25 mg/m2 plus epirubicin 100 mg/m2 on days 29 and 43. Patients with an objective response on day 56 then received another cycle of gemcitabine/docetaxel on day 57 and of vinorelbine/epirubicin on day 71. Conservative surgery was scheduled for all patients. RESULTS: Of the patients enrolled, 30% had triple-negative breast cancer (TNBC). The pathologic complete response (pCR) rate was 22% overall, but was higher in TNBC than patients without TNBC (40.9% vs 14.0%; p = 0.028). Among patients with a pCR, patients with TNBC had similar recurrence-free survival (RFS) and overall survival (OS) to patients without TNBC. Among those without a pCR, RFS rates for patients with TNBC were significantly lower than for patients without TNBC (p = 0.04). The most common severe hematologic toxicity was neutropenia. CONCLUSIONS: Administering four drugs in a dose-dense alternating sequence gave a high pCR in patients with operable, invasive breast cancer. Patients with TNBC with a pCR had similar OS to patients without TNBC, whereas patients with TNBC without a pCR had poorer survival rate than their non-TNBC counterparts.

Reduced versus full doses of irradiation after 3 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine in early stage Hodgkin lymphomas: results of a randomized trial.

BACKGROUND: The combination of 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and a tailored, extended irradiation schedule has been used to treat patients with early Hodgkin lymphoma (HL) in the authors' group since 1981. The randomized H97-E trial (1997-2004) was designed to assess the impact of a slightly reduced irradiation dose on the freedom from treatment failure (FFTF) rate. METHODS: Patients with supradiaphragmatic HL at clinical stages I and II who had

What is the real impact of bone pain on survival in patients with metastatic hormone-refractory prostate cancer treated with docetaxel?

OBJECTIVES: To determine the benefit of starting early chemotherapy with docetaxel (the recommended first-line treatment) for patients with asymptomatic metastatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Data were analysed from 145 patients with HRPC treated with chemotherapy between February 2000 and June 2002 in one French centre. Eligible patients were categorized into three groups according to the bone pain at baseline, i.e. minimal/no pain, mild, and moderate/severe pain. The primary endpoint was the effect of bone pain on overall survival (OS). RESULTS: Docetaxel was administered to 67% of patients. The risk of death was 1.56 and 2.11 times higher for patients with mild or moderate/severe pain than for those with minimal/no pain (P = 0.027). The median (95% confidence interval (CI)) OS was 23.1 (18.5-27.6) and 14.1 (8.9-19.2) months (P = 0.001, log-rank-test) for patients with minimal pain or no pain treated with docetaxel-based chemotherapy compared with mitoxantrone, respectively. The prostate-specific antigen doubling time (PSA-DT) had a significant effect on OS in patients with minimal/no pain, with a median of 32.4 and 16.5 months for a PSA-DT of >or=45 and <45 days, respectively (P < 0.001). CONCLUSIONS: Our results suggest that patients with HRPC and minimal or no bone pain could have better survival than those with mild pain or moderate to severe pain, independent of the treatment administered. In addition, patients with HRPC and minimal or no bone pain treated with docetaxel-based chemotherapy have a significantly better OS than those treated with mitoxantrone. The PSA-DT can be useful to identify asymptomatic patients who are candidates for early treatment.

Salvage therapy with bevacizumab-sunitinib combination after failure of sunitinib alone for metastatic renal cell carcinoma: a case series.

We present a case series of seven patients with metastatic renal cell carcinoma treated with bevacizumab (10 mg/kg) in combination with sunitinib 25-50 mg as salvage therapy after disease progression under sunitinib monotherapy. Two patients had a partial response, four had stable disease, and one patient had disease progression. After a median follow-up of 17.2 mo, median progression-free survival and overall survival were 8.5 and 15.1 mo, respectively. Two patients experienced exacerbation of their preexisting hypertension; there were no grade 4 toxicities. The bevacizumab-sunitinib combination in sunitinib-refractory patients seems active and has a tolerable toxicity profile.

Early versus late intensification for patients with high-risk Hodgkin lymphoma-3 cycles of intensive chemotherapy plus low-dose lymph node radiation therapy versus 4 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine plus myeloablative chemotherapy with autologous stem cell transplantation: five-year results of a randomized trial on behalf of the GOELAMS Group.

BACKGROUND: The 5-year freedom from treatment failure (FFTF) rate, with treatment failure defined as the lack of post-treatment complete remission (CR), recurrence, or death, ranges from 60% to 70% after 6 to 8 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), which is the reference treatment for patients with advanced Hodgkin lymphoma (HL). In this randomized, phase 2 study, the authors tested 2 intensive chemotherapy regimens in 158 patients with clinical stage (CS) IIB through IV HL accompanied by high-risk factors who were recruited between May 1997 and December 2004. METHODS: High-risk CS IIB, III, and IV were defined by the presence of > or =5 involved lymphoid areas, and/or a mediastinal mass ratio > or =0.45, and/or > or =2 extra lymph node sites affected by the disease (for CS IV). In Arm V, 82 patients received 3 courses of combined vindesine (5 mg/m(2)), doxorubicin (99 mg/m(2)), carmustine (140 mg/m(2)), etoposide (600 mg/m(2)), and methylprednisolone (600 mg/m(2)) (VABEM) followed by low-dose lymph node irradiation. In Arm A, 76 patients received 4 cycles of ABVD followed by myeloablative combined carmustine (300 mg/m(2)), etoposide (800 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)) and underwent autologous stem cell transplantation. RESULTS: After 3 cycles of VABEM, the CR rate was 89% versus 60% after 4 cycles of ABVD. However, after the completion of treatment, the CR rates for Arms V and A were similar (89% and 88%, respectively). The 5-year FFTF rates for Arms V and A also were similar (79% and 75%, respectively) along with the 5-year overall survival rates (87% and 86%, respectively). CONCLUSIONS: Early intensification (Arm V) and late intensification (Arm A) were equally effective for treating patients with high-risk/advanced HL.

Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced onycholysis and cutaneous toxicity of the foot.

BACKGROUND: Onycholysis occurs in approximately 30% of patients treated with docetaxel. The efficacy and safety of an Elasto-Gel frozen sock (FS) was investigated for the prevention of docetaxel-induced nail and skin toxicity of the feet. METHODS: Patients receiving docetaxel at a dose of 70 to 100 mg/m(2) every 3 weeks were eligible for this matched case-control study. Each patient wore an FS for 90 minutes on the right foot. The unprotected left foot acted as control. Nail and skin toxicities were assessed using National Cancer Institute Common Toxicity Criteria (version 3) and compared using a 2-sample Wilcoxon matched-pairs rank test adjusted for tied values. RESULTS: Fifty consecutive patients were included between April 2005 and January 2007. Nail toxicity was significantly lower in the FS-protected foot compared with the control foot (grade 0: 100% versus 79%; and grade 1 and 2: 0% versus 21%, respectively) (P= .002). Skin toxicity was grade 0: 98% versus 94%; and grade 1 and 2: 2% versus 6% in the FS-protected and the control feet, respectively. The median times until toxicity occurrence were not found to differ significantly between the groups. One patient experienced discomfort because of cold intolerance. CONCLUSIONS: Cold therapy using FS significantly reduced the incidence of docetaxel-induced foot nail toxicity, as previously demonstrated using frozen gloves for the hands.

Twenty-year disease and treatment-associated mortality rates of patients with Hodgkin lymphoma of clinical stages IIIB and IV prospectively treated with 3-month anthracycline-based chemotherapy followed by extended high-dose radiation.

BACKGROUND: In 1981, the authors developed an original strategy combining 3 cycles of doxorubicin (adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) or ABVD-like chemotherapy and extended high-dose radiation for treating patients with clinical stages IIIB and IV Hodgkin lymphoma (HL). In the current study, the authors analyzed the 20-year results of this treatment as applied to 213 patients according to 2 successive trials. METHODS: All patients who responded to chemotherapy received extended high-dose radiation. The rates of complete remission (CR), freedom from disease progression (FFP), HL-specific survival (HLSS), second tumors and cardiac events, freedom from treatment-associated mortality (FFTM), overall survival (OS), and event-free survival were calculated. RESULTS: In December 2006, the median follow-up of the surviving patients exceeded 13 years; 102 patients (48%) achieved a CR after chemotherapy and 178 patients (84%) did so after radiotherapy. The rates of FFP (61%, quasi-stable after 6 years) and HLSS (81.6%, stable after 12 years) were found to be significantly higher in patients who achieved a CR after chemotherapy. The incidence of hematologic malignancies was 10.9% (with 10 of 12 events occurring within the first 7 years). The rates of solid tumors (32.4%), cardiac events (33.4%), and FFTM (65.6%) did not reach any plateau by 20 years and were found to be significantly associated with patient age. The 20-year OS rate was 48%. CONCLUSIONS: This combined modality treatment gave long-term results similar to those obtained using 6 to 8 cycles of ABVD. Response to the initial brief chemotherapy administration was found to be predictive of the FFP and HLSS rates. The low rate of FFTM was the result of extended high-dose radiation. The results of the current study should help to design future trials for treating patients with advanced stages of HL.

Meta-analysis of randomised trials comparing gemcitabine-based doublets versus gemcitabine alone in patients with advanced and metastatic pancreatic cancer.

OBJECTIVE: To evaluate the impact on overall survival at 6, 12 and 18 months of gemcitabine-based doublets compared with gemcitabine alone in patients with advanced and metastatic pancreatic cancer. METHODS: We conducted a systematic review and meta-analysis of published data on the use of gemcitabine-based doublets compared with gemcitabine alone in chemotherapy-naive patients with advanced and metastatic pancreatic cancer treated in randomised controlled phase II-III trials with overall survival as the principal or secondary endpoint. To this end, a literature search was performed using Cochrane methodology. The relative risks with 95% confidence intervals were estimated based on adjusted number of deaths and patients at risk according to the extent of follow-up and censoring. Twenty-three randomised clinical trials including 5886 patients met the inclusion criteria. In these trials, 2932 patients were randomly assigned to receive gemcitabine-based doublets and 2954 patients to receive gemcitabine alone. RESULTS: Gemcitabine-based doublets were associated with small but significant reductions in the risk of death at 6, 12 and 18 months of 8% (95% CI 3, 13), 4% (95% CI 2, 7) and 3% (95% CI 1, 5), respectively (p<0.005 for all timepoints). No heterogeneity between studies was observed. Subgroup analyses showed an overall survival benefit for gemcitabine-based doublets in clinical trials testing the same planned dose intensity of gemcitabine in comparative arms, using platinum salt-based protocols and with survival as the primary endpoint. CONCLUSION: This meta-analysis of data obtained from randomised controlled phase II-III trials of patients with advanced pancreatic cancer showed a small but significant improvement in overall survival for patients receiving gemcitabine-based doublets compared with gemcitabine alone.

Serum PSA half-life as a predictor of survival for hormone-refractory prostate cancer patients: modelization using a standardized set of response criteria.

OBJECTIVE: Changes of serum prostate-specific antigen (PSA) during chemotherapy have been validated as a marker of response for hormone-refractory prostate cancer (HRPC) patients. We retrospectively established new response criteria to assess the risk of death. METHODS: Two hundred fifty-six chemonaive HRPC patients treated with chemotherapy were included in the analysis. According to PSA half-life (HL) dynamics, three response categories were defined: responders (R), late-progressors (LP) and initial-progressors (IP), that were compared with Working Group (WG) criteria. PSA HL time to failure (TTF) and overall survival (OS) were estimated and compared between HT categories. Multivariate regression analysis was performed to isolate the impact on OS of these response categories. A new predictor of survival, delta-time PSA interval (DeltaT) was described. RESULTS: PSA HL categories were strongly related with WG criteria (P = 0.0001). PSA HL TTF differed among PSA HL categories: 4.2, 2.3, and 0.9 months for R, LP, and IP patients, respectively, and their respective median OS were 27, 19.7, and 12.3 months (P = 0.0001). For DeltaT > or = 3 versus <3 months, median OS significantly differed: 24.9 months versus 13.2 months (P = 0.0001). CONCLUSIONS: PSA HL dynamics during chemotherapy were able to accurately predict survival, earlier than WG-defined progression criteria. This criterion should be prospectively evaluated in randomized trials for HRPC patients in order to better estimate the risk of death.

Predictive and discriminating three-risk-group prognostic scoring system for staging Hodgkin lymphomas.

BACKGROUND: Several 3-stage Ann Arbor classification-derived prognostic systems were constructed since 1980 to identify the prognosis of Hodgkin lymphoma (HL). Modern statistical tools were applied to 955 patients treated between 1981 and 1996 to build a 3-stage prognostic scoring system (PSS). METHODS: Each variable associated with 10-year overall survival (10-year OS) was assigned to 2 (0 or 1) or 3 (0, 1 or 3) values. By summing the values attributed to each variable, 3 stages were defined. 10-year OS, 5-year event-free survival (5-year EFS), and freedom from progression (5-year FFP) rates of the PSS and of other existing systems were then compared. RESULTS: Four variables were associated with 10-year OS: age (<40 = 0, >or=40 = 1), number of involved lymphoid areas (1-2 = 0, 3-4 = 1, >or=5 = 2), visceral disease (no = 0, yes = 1), and systemic symptoms (no = 0, yes = 1). Scores 0 and 1, 2 and 3, and >or=4 were attributed to 59.7%, 30.9%, and 9.4% of the patients who had 10-year OS rates of 93.5, 75.7, and 53.4% and 5-year EFS / 5-year FFP rates of 91.2%/90.3%, 78.1%/76.3%, and 54.1%/52.6%, respectively. The discrimination and prediction abilities of the PSS were better than those of the other systems tested; moreover, the PSS adequately identified the few patients with a worse prognosis without resorting to the International Prognostic Score for advanced stages. The PSS was also highly predictive for 489 patients treated between 1997 and 2002. CONCLUSION: PSS is a useful alternative to the existing prognostic systems for evaluating HL patients.

Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis and cutaneous toxicity of the hand.

PURPOSE: Onycholysis and skin toxicity occur in approximately 30% of patients treated with docetaxel. We investigated the efficacy and safety of an Elasto-Gel (84400 APT Cedex, Akromed, France) frozen glove (FG) for the prevention of docetaxel-induced onycholysis and skin toxicity. PATIENTS AND METHODS: Patients receiving docetaxel 75 mg/m2 alone or in combination chemotherapy were eligible for this case-control study. Each patient wore an FG for a total of 90 minutes on the right hand. The left hand was not protected and acted as the control. Onycholysis and skin toxicity were assessed at each cycle by National Cancer Institute Common Toxicity Criteria and documented by photography. Wilcoxon matched-pairs rank test was used. RESULTS: Between August 2002 and September 2003, 45 patients were evaluated. Onycholysis and skin toxicity were significantly lower in the FG-protected hand compared with the control hand (P = .0001). Onycholysis was grade (G) 0 in 89% v 49% and G1 to 2 in 11% v 51% for the FG-protected hand and the control hand, respectively. Skin toxicity was G0 in 73% v 41% and G1 to 2 in 27% v 59% for the FG-protected and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between the FG-protected and the control hand, respectively (106 v 58 days for nail toxicity; 57 v 58 days for skin toxicity). Five patients (11%) experienced discomfort due to cold intolerance. CONCLUSION: FG significantly reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management to improve a patient's quality of life.

Multicenter randomized phase II study of two schedules of docetaxel, estramustine, and prednisone versus mitoxantrone plus prednisone in patients with metastatic hormone-refractory prostate cancer.

PURPOSE: Mitoxantrone-corticosteroid is currently the standard palliative treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical trials documented the high activity of the docetaxel-estramustine combination. We conducted a randomized phase II study to evaluate prostate-specific antigen (PSA) response (primary end point) and safety of two docetaxel-estramustine-prednisone (DEP) regimens and mitoxantrone-prednisone (MP). PATIENTS AND METHODS: One hundred thirty metastatic HRPC patients were randomly assigned to receive docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 and 9 of each 21-day cycle) and estramustine (280 mg p.o. tid on days 1 through 5 and 8 through 12) or mitoxantrone 12 mg/m2 every 3 weeks; all patients received prednisone (10 mg daily). RESULTS: One hundred twenty-seven patients were assessable for PSA response and safety. A > or = 50% PSA decline was found in a greater percentage of patients in the docetaxel arms (67% and 63%) compared with MP (18%; P = .0001). Median time to PSA progression was five times longer with DEP than with MP (8.8 and 9.3 v 1.7 months, respectively; P = .000001). Overall survival was better in the docetaxel arms (18.6 and 18.4 months) compared with the MP arm (13.4 months), but not significantly so (P = .3). Crossover rates differed significantly among treatment arms (16%, 10%, and 48% in arms A, B, and C, respectively; P = .00001). Treatment-related toxicities were mild and mainly hematologic. CONCLUSION: The results of this randomized phase II study showed significantly higher PSA decline < or = 50% and longer times to progression in HRPC patients receiving DEP-based chemotherapy than MP, and that DEP could be proposed in this setting.

Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation.

Lymphocyte-predominant Hodgkin lymphoma (LPHL), according to the Revised European-American Lymphoma classification, was considered on a retrospective basis as a specific clinical entity with a large majority of patients at clinical stage (CS) IA or IIA. Of the 500 patients with CS IA/IIA Hodgkin lymphoma (HL) prospectively treated between 1981 and 1996 by one or 3 courses of anthracycline-based chemotherapies combined with high-dose extended irradiation, disease in 42 patients was reclassified as LPHL. These 42 patients, none of whom had mediastinal involvement (MI), were compared with the 458 patients with classical HL (cHL), 144 without MI and 314 with MI. Surprisingly, the male-female ratio, age, first site involved, hemoglobin level, lymphocyte count, and sedimentation rate of patients with LPHL and cHL without MI were identical and significantly different from those of patients with cHL with MI. Moreover, 15-year HL mortality rates were similarly low in patients with LPHL (2.4%) and cHL without MI (0.7%). Overall survival rates were also similar (86% and 82%) and as high as 100% and 95% in patients treated before the age of 40 years. This study demonstrated that LPHL and cHL without MI shared the same presenting characteristics and the same excellent long-term prognosis after a brief anthracycline-based chemotherapy plus high-dose extended irradiation.

Three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or epirubicin, bleomycin, vinblastine, and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial.

From 1990 to 1996, a total of 386 adult patients with early/intermediate Hodgkin disease (HD) were randomly assigned to receive 3 cycles of adriamycin, bleomycin, vinblastine, dacarbazine (an alkylating agent), and methylprednisolone (ABVDm, arm A) or epirubicin, bleomycin, vinblastine, methotrexate, and methylprednisolone (EBVMm, arm E), a combination without alkylating agent. Responding patients received extended field radiation therapy (RT). Postchemotherapy complete remission and 10-year freedom from progression rates were higher in arm A (79.5% and 91.4%) than in arm E (70.4%, P =.04, and 80%, P <.002). HD mortality (HDM), treatment-related mortality (TRM), and overall survival (OS) were similar in both arms (A, 2.1%, 7.5%, and 90.4%; B, 3.9%, 5.5%, and 90.3%). However TRM and OS rates were lower in patients aged 40 years or older (P <.005), reflecting the increasing incidence of background fatal events with increasing age. Finally, event-free survival (EFS) was higher in arm A (84.6%) than in arm E (74.9%, P <.02). In patients aged younger than 40 years in arm A (74%), 10-year EFS and OS rates were 88.9% and 95.4% with HDM and TRM rates as low as 0.7% and 3%. Three courses of ABVDm plus RT are the best available option for treating early or intermediate HD.

The biological meaning of anti-HBC positive result in blood donors: relation to HBV-DNA and to other serological markers

In order to assess the potential risk of anti-HBc-positive blood donors for post-transfusional hepatitis and to investigate whether other HBV serological markers are capable of identifying the presence of the virus, 1000 first-time blood donors were enrolled between June and July 1997. These donors were screened using routine Brazilian blood center tests (HIV 1 and 2, HTLV 1 and 2, Chagas disease, Syphilis, HCV, HBsAg, anti-HBc and ALT ). The 120 (12 percent) found to be anti-HBc-positive underwent further tests: HBe, anti-HBe, anti-HBs and HBV-DNA by PCR. Ten cases were HBsAg positive and all were HBV-DNA positive by PCR. Three HBsAg-negative donors were HBV-DNA-positive. Two HBV-DNA-positive donors were also anti-HBs-positive. All the HBV-positive donors had at least one HBV marker other than anti-HBc. Anti-HBc is an important cause of blood rejection. Testing for HBsAg alone is not fully protective and anti-HBc remains necessary as a screening test. The presence of anti-HBs is not always indicative of absence of the virus. The addition of other HBV serological markers could represent an alternative in predicting the presence of the virus when compared with PCR. It is recommended that other studies should be carried out to confirm this finding

Treatment of patients with advanced or bulky Hodgkin disease with a 12-week doxorubicin, bleomycin, vinblastine, and dacarbazine-like chemotherapy regimen followed by extended-field, full-dose radiotherapy: long-term results of the Groupe Ouest et Est des Leucémies et Autres Maladies de Sang H90-A/B Multicenter Randomized Trial.

BACKGROUND: This Phase II study was performed in patients with advanced or bulky Hodgkin disease (HD) to evaluate the results of a 7-drug chemotherapy (CT) regimen that was administered over 12 weeks according to 2 randomized modalities followed by high-dose lymph node irradiation. METHODS: From 1990 to 1996, 162 patients with HD at clinical stages (CS) I-III with bulky disease (mediastinal mass ratio >or= 0.45 and/or unilateral or bilateral pelvic plus lumboaortic disease; 86 patients) or CS IV (76 patients) were randomized to receive the same cumulated dose of a CT regimen consisting of epirubicin (240 mg/m(2)), bleomycin (60 mg/m(2)), vinblastine (20 mg/m(2)), vincristine (4 mg/m(2)), cyclophosphamide (4000 mg/m(2)), etoposide (900 mg/m(2)), and methotrexate (180 mg/m(2)) plus methylprednisolone (1500 mg/m(2)) over 12 weeks either every 4 weeks (Arm Y, 79 patients) or every 3 weeks (Arm Z, 83 patients). Patients with disease in complete remission (CR) or partial remission after CT received extended-field lymph node irradiation (involved areas, 40 grays [Gy]; noninvolved areas, 30 Gy). RESULTS: Forty-two percent of patients achieved a post-CT CR, and 86% of patients achieved a CR after the completion of irradiation (there was no difference between Arm Y and Arm Z). Thirty-five patients developed recurrent disease; most of those patients were in post-CT partial remission. The 10-year freedom from first progression rate was 63.9% (there was no difference between Arm Y and Arm Z). Thirty-eight patients died: 24 patients from HD, 3 patients from CT-related early sepsis, 1 patient from radiation-induced pneumonitis, 6 patients from a second malignancy, and 4 patients from causes unrelated to treatment. The overall 10-year survival rate was 76.7%. Survival was slightly higher among patients in Arm Y (83.3%) compared with patients in Arm Z (70.2%; P = 0.12). CONCLUSIONS: No differences were found when the same amount of CT was delivered in three courses or in four courses. In 1997, because most recurrences of the H90-A/B trial occurred in patients who achieved a post-CT partial remission, the authors decided to reinforce the intensity of the initial CT and designed a new randomized study comparing two modalities of more intensive CT plus consolidative radiotherapy (H97-LM trial).

Fifteen-year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy plus high-dose irradiation.

Between 1972 and 1988, 869 adult patients received MOPP (mechlorethamine, vincristine, procarbazine and prednisone; 462 patients) or ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine; 373 patients) and subsequent high-dose irradiation for Hodgkin's disease. Nine patients developed a leukaemia after MOPP and four after ABVD; 11 patients were diagnosed as acute non-lymphoblastic leukaemia (ANLL) and two as acute lymphoblastic leukaemia (ALL). Both cases of ALL were observed after ABVD and were associated with a 11q23 translocation. The 15-year actuarial risk of secondary leukaemia was 2.4% for the whole group of patients, 3.4% after MOPP and 1.3% after ABVD. For the MOPP subgroup, the risk of leukaemia was significantly associated with the extent of irradiation: 2.4% for limited irradiation and 13.9% for extended irradiation (P < 0.001). For the ABVD subgroup, this risk remained low (1.3%) whatever the type of irradiation. Concerning ANLL, the MOPP regimen was significantly associated with a higher risk: 3.4% versus 0.7% for ABVD (P

Expression of genes involved in chemoresistance, proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome.

This study investigated the multidrug resistance, proliferation and apoptosis expression in renal cell carcinomas compared to adjacent normal kidney (ANK) tissues. Multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi), Topoisomerase-II alpha (TOPO-IIalpha), thymidylate synthase (TS), thymidine kinase (TK), Ki67, BAX and BCL-2 genes were analysed in a series of 30 renal cell carcinomas (RCC) and 16 biopsies from adjacent normal kidney (ANK) tissue using reverse-transcription-PCR (rt-PCR). The mean MDR1 expression was significantly lower in RCC than that of ANK (0.4 +/- 0.2 sd versus 0.75 +/- 0.19, p = 0.0008). The expression of MRP, GST-pi and TOPO-IIalpha was not significantly different in RCC as compared with ANK. The mean TK expression in RCC was significantly higher than in ANK (0.31 +/- 0.15 versus 0.09 +/- 0.08, p = 0.002). The TS and Ki67 expression in RCC was significantly higher than in ANK (87.5%, IC95% 71-100% versus 0%, p = 0.001; 56% IC95% 32-81% versus 0%, p = 0.004, respectively). BAX and BCL-2 expression in RCC was significantly higher than that of ANK (0.51 +/- 0.08 versus 0.18 +/- 0.12, p = 0.0001; 0.73 +/- 0.16 versus 0.5 +/- 0.22, p = 0.01, respectively). No significant correlation was found between MDR1, MRP, GST-pi, TOPO-IIalpha, TS, TK and BAX expression with the grade and the clinical stage in RCC.