Influence of the implementation of a multidisciplinary consultation program on adherence to the first ever course of oral antineoplastic treatment in patients with cancer.

PURPOSE: To evaluate adherence (as measured by the medication possession ratio) to the first ever course of oral antineoplasic treatment in cancer patients before and after the implementation of a multidisciplinary consultation program (involving an oncologist, a pharmacist, and a nurse) and to investigate the program's impact on adverse events and drug-related problems. PATIENTS AND METHODS: In a retrospective single-center study, we compared the medication possession ratio 2 months after treatment initiation in a control group (before multidisciplinary consultation program implementation) versus an interventional group (after multidisciplinary consultation program implementation). RESULTS: Two months after oral antineoplasic treatment initiation, the mean ± standard deviation medication possession ratio did not differ significantly when comparing the interventional (multidisciplinary consultation program) group (n = 33; 0.99 ± 0.06) with the control group (n = 64; 0.94 ± 0.16) (p = 0.062). Patients in the multidisciplinary consultation program group had fewer adverse events in general (41, vs 109 in the control group; p = 0.048) and digestive adverse events in particular (6 vs 29, respectively; p = 0.007). A total of 53 and 40 drug-related problems were identified in the control and multidisciplinary consultation program groups, respectively (p = 0.074). CONCLUSIONS: Implementation of an multidisciplinary consultation program was not associated with a significant difference in drug adherence (as assessed by the medication possession ratio), which was good before and after implementation. The multidisciplinary consultation program was associated with a lower incidence of adverse events.

Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95.

Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.

Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support.

BACKGROUND: The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown. METHODS: We compared high-dose therapy plus autologous stem-cell support with the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in a randomized trial. The patients were 15 to 60 years of age, had untreated aggressive lymphoma, and were at low, low intermediate, or high intermediate risk of death (i.e., a maximum of two adverse prognostic factors) according to the age-adjusted International Prognostic Index. The primary outcome was event-free survival at five years. RESULTS: Of 207 consecutive patients, 197 underwent randomization; 99 were assigned to receive CHOP, and 98 to receive high-dose chemotherapy plus stem-cell transplantation. Overall, 78 percent of the patients completed the assigned treatment; the median follow-up was four years. The estimated event-free survival rate (+/-SD) at five years was significantly higher among patients who received high-dose therapy than among patients who received CHOP (55+/-5 percent vs. 37+/-5 percent, P=0.037). Among patients with a high intermediate risk of death, according to the age-adjusted International Prognostic Index, the five-year survival rate was significantly higher after high-dose therapy than after CHOP (74+/-6 percent vs. 44+/-7 percent, P=0.001). CONCLUSIONS: High-dose chemotherapy with autologous stem-cell support is superior to CHOP in adults with disseminated aggressive lymphoma.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results.

PURPOSE: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. METHODS AND MATERIALS: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. RESULTS: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). CONCLUSIONS: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.

Subcutaneous interleukin-2 and interferon alfa administration in patients with metastatic renal cell carcinoma: final results of SCAPP III, a large, multicenter, phase II, nonrandomized study with sequential analysis design--the Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE: This outpatient multicenter trial tested the hypothesis that subcutaneous administration of an interleukin-2 (IL-2)/interferon alfa (IFN alpha) combination produces a response rate greater than 20% in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC received a 12-week induction treatment with subcutaneous IL-2 (5 days/wk, 9 and 18 million U/d)/IFN alpha (3 days/wk, 6 million U/d). After evaluation, patients with objective response or stable disease were randomly assigned to maintenance treatment or short consolidation treatment. RESULTS: Lack of benefit was shown at the 12th sequential analysis, and the trial was closed. At the end of the induction period, 26 (21%) of 122 patients had objective responses (including six complete responses). Thirty-three patients (27%) developed severe toxicity requiring dose reductions, delayed treatment, or treatment termination. Survival rates at one, two, and four years were 63%, 38%, and 17%, respectively. Three-year survival was 20% in patients with two poor prognosis factors and 37% in patients with one or no poor prognosis factors (P =.016). Three-year survival was significantly better (P < 10-3) in patients with erythrocyte sedimentation rate less than 35 mm (43%) compared with those with 1-hour sedimentation rate greater than 35 mm (19%). CONCLUSION: This study confirms the importance of prognostic factors when initiating cytokine immunotherapy in patients with metastatic RCC and underlines the prognostic value of erythrocyte sedimentation rate before treatment initiation. Nonetheless, this subcutaneous IL-2/IFN alpha combination does not improve response rate or survival compared with subcutaneous IL-2 alone, although a definitive conclusion cannot be drawn in the absence of a randomized study comparing the two treatments.

Stage I-IIE primary non-Hodgkin's lymphoma of the testis: results of a prospective trial by the GOELAMS Study Group.

Sixteen patients with aggressive primary testicular involvement were analyzed separately from a prospective multicenter series of 494 patients with stage I/II aggressive nonlymphoblastic lymphoma. The treatment strategy included 3 cycles of anthracycline-based chemotherapy followed by regional radiation therapy on inguinal, iliac, and para-aortic lymph nodes and central nervous system (CNS) prophylaxis by intrathecal chemotherapy and brain irradiation. Chemotherapy was stratified by age group. Patients aged 18-60 years received the Groupe Ouest Est d'Etude des Leucemies Aigues et Maladies du Sang (GOELAMS) 02 protocol: 3 monthly cycles of VCAP (vindesine 3 mg/m2 day 1, doxorubicin 80 mg/m2 day 2, cyclophosphamide 1500 mg/m2 day 2, and prednisone 80 mg/m2 days 1-5). Patients aged 61-75 years received the GOELAMS 03 protocol: 3 monthly cycles of VECP-Bleo (vindesine 3 mg/m2 day 1, epirubicin 60 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, prednisone 50 mg/m2 days 1-7, and bleomycin 10 mg/m2 days 1 and 5). Sixteen patients had testicular involvement (3.3%). Median age was 62 years (range, 29-73 years). The histological subtypes were diffuse large-cell lymphoma in all cases. Ann Arbor stage was IEA in 11 patients, IEB in 3 patients, and IIEA in 2 patients. All patients achieved a complete response. One patient died from septic shock during the last course of chemotherapy. After a median follow-up period of 73.5 months, the probability of disease-free survival (DFS) and overall survival (OS) were 70% and 65%, respectively for all patients. Disease-free survival and OS were 66% and 83% in patients = 60 years of age, and 74% and 56% in patients > 60 years of age. Relapse occurred in extranodal sites in 4 cases and in abdominal lymph nodes in the last case. Relapse in the CNS occurred in only 1 patient and in the contralateral testis in 1 patient. We found no correlation between OS, DFS and extent of testicular involvement, Ann Arbor stage, International Prognostic Index score, or lactate dehydrogenase level. This is the first report of a prospective study in which treatment of testicular non-Hodgkin's lymphoma was precisely defined at diagnosis. Compared to other series, a combination of orchiectomy with 3 cycles of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-derived chemotherapy, regional radiation therapy, and CNS prophylaxis seems to improve prognosis. The improvement in prognosis seemed to be due in part to irradiation, including the pelvic and lomboaortic lymphatic areas, and in part to CNS prophylaxis.