Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherapy.

Background: In 2006 the 5-yr results of the BIG 2-98 trial suggested better disease-free survival (DFS) in the sequential docetaxel arm compared with both the combination doxorubicin-docetaxel arm (HR 0.83) and the sequential doxorubicin-based control arm (HR 0.79) in patients with node-positive (N+) breast cancer (Francis et al, JNCI 2008,100:121-133).Methods: Treatment (in mg/m2) was given intravenously every 3 weeks unless otherwise stated.Arm 1: doxorubicin (A) 75 × 4 → CMF × 3 (oral cyclophosphamide (C) 100 days 1-14, methotrexate 40 and 5FU 600 days 1 and 8, q 28 days); Arm 2: AC 60/600 × 4 → CMF × 3; Arm 3: A 75 × 3 → docetaxel (T) 100 × 3 → CMF × 3; Arm 4: AT 50/75 × 4 → CMF × 3. Randomization was in the ratio (1:1:2:2). Endocrine and radiotherapy were administered subsequently as per local guidelines. No indications for adjuvant trastuzumab were available when the trial was recruiting. Hereunder we report the updated results at a median follow-up of 8 years.Results: 2,887 patients were enrolled between June '98 and June '01 by 173 centers in 21 countries and 9 BIG groups. In May '09 median follow-up was 93.4 months and total number of events was 916. For the primary comparison (A → T + AT vs. A+AC) DFS was similar (HR 0.91; 95% CI 0.80-1.05). However, DFS appeared significantly better when docetaxel was given sequentially (A → T) compared with control (A) (HR 0.81; 95% CI 0.67-0.99) and compared with combination (AT) (HR 0.84; 95% CI 0.72-0.99). Overall survival (OS) was not significantly better overall (HR 0.91; 95 % CI 0.77-1.08), but appeared significantly better when docetaxel was given sequentially (A → T) compared with combination (AT) (HR 0.79; 95% CI 0.65-0.98) (Table 1). Analyses based on central pathology review defining 4 breast cancer sub-types (highly or incompletely endocrine-responsive, triple negative, HER2 +) and also taking into account patient age and ovarian function are being performed and will be presented at the meeting.Discussion: These data suggest that docetaxel given sequentially after doxorubicin may provide a survival benefit in N+ breast cancer and lend some support to the Norton-Simon hypothesis, which predicted that drug resistance might be overcome by sequential delivering of cytotoxic agents at the maximally tolerated dose. Results by molecular sub-type might provide information on patient cohorts deriving the largest benefit from T.[Table 1. Hazard Ratio (HR) and 95 % CI for DFS and OS]ComparisonHRs for DFS [95% C.I.] p-valueHRs for OS [95% C.I.] p-valueA-T+AT vs A+AC (primary)0.91 [0.80 - 1.05] 0.1870.91 [0.77 - 1.08] 0.28A-T vs A (secondary)0.81 [0.67 - 0.99] 0.0360.86 [0.67 - 1.11] 0.24AT vs AC (secondary)1.02 [0.84 - 1.23] 0.850.96 [0.76 - 1.21] 0.71A-T vs AT (secondary)0.84 [0.72 - 0.99] 0.0350.79 [0.65 - 0.98] 0.028  Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 601.

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New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m(2) for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later.

En esta conferencia se tratará los siguientes aspectos de las terapias biológicas: 1. Éxitos de las terapias moleculares. 2. Obstáculos en su aplicación. 3. Mirando hacia el futuro. 4. Reflexión final.