Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial

Background: Oral capecitabine achieves a superior response rate with an improved safety profile compared with bolus 5-fluorouracil-leucovorin (5-FU/LV) as first-line treatment for patients with metastatic colorectal cancer. We report here the results of a large phase III trial investigating adjuvant oral capecitabine compared with 5-FU/LV (Mayo Clinic regimen) in Dukes' C colon cancer. Patients and methods: Patients aged 18-75 years with resected Dukes' C colon carcinoma were randomized to receive 24 weeks of treatment with either oral capecitabine 1250 mg/m2 twice daily, days 1-14 every 21 days (n = 993), or i.v. bolus 5-FU 425 mg/m2 with i.v. leucovorin 20 mg/m2 on days 1-5, repeated every 28 days (n = 974). Results: Patients receiving capecitabine experienced significantly (P <0.001) less diarrhea, stomatitis, nausea/vomiting, alopecia and neutropenia, but more hand-foot syndrome than those receiving 5-FU/LV. Fewer patients receiving capecitabine experienced grade 3 or 4 neutropenia, febrile neutropenia/sepsis and stomatitis (P <0.001), although more experienced grade 3 hand-foot syndrome than those treated with 5-FU/LV (P <0.001). Capecitabine demonstrates a similar, favorable safety profile in patients aged <65 years or ≥65 years old. Conclusions: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in 2004. Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cance

Fluorouracil leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer

Purpose This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated. Patients and Methods Patients received cetuximab (400 mg/m(2) initial dose followed by 250 mg/m(2)/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m(2) on day 1, plus leucovorin 200 mg/m(2) and fluorouracil as a 400 mg/m(2) bolus followed by a 600 mg/m(2) infusion during 22 hours on days 1 and 2; n = 169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n = 233). Results The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio = 1.52; P = .064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated. Conclusion KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer

Magnetic Birefringence Study of the Magnetic Core Structure of Ferritin

Magnetically induced optical birefringence (Δ n) was measured for magnetoferritin and horse spleen ferritin aqueous suspensions. The Δ n for magnetoferritin was described in the frame of the Langevin formalism taking into account distribution of core diameter. The established average magnetic dipole moment and core diameter is equal to about 460 $μ_{B}$ and 3 nm, respectively. It was shown that magnetic birefringence and the Cotton-Mouton constant can be powerful parameters in identification of the magnetic core structure of ferritin, especially useful in biomedicine

MAGNETOOPTICAL SPECTROSCOPY OF THE Q TRANSITION OF ZINC TETRABENZOPORPHYRIN ISOLATED IN AN ARGON MATRIX.

Author Institution: Department of Chemistry, University of Canterbury; Department of Chemistry, University of VirginiaAbsorption, fluorescence, magnetic circular dichroism (MCD), magnetic circularly polarized luminscence (MCPL) and longitudinal Zeeman spectra were measured for the $Q(^{1}A^{1}_{g}(\pi)) \rightarrow ^{1}E_{u}(\pi^{*}e)$ transition of zinc tetra benzoporphyrin isolated in an argon matrix (ZnTBP/Ar). Moment analysis of the MCD and absorption yield an excited-state orbital g value of $g_{1} = 7.7 \pm 0.4$. The large value of this parameter is consistent with a four-orbital interpretation of the Q transition for metallophthalocyanines. The magnetic field dependence of the zero-phonon Zeeman shifts and moment analysis of the emission spectra independently yield information concerning Jahn-Teller (JT) effects in the excited state. These data have been interpreted in the context of a single effective JT-active coordinate and local crystal-field distortions of both $b_{1}g$ and $b_{2}g$ symmetry. [FIGURE]

A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients.

International audienceBACKGROUND: XRP6258 is a novel taxoid with a low affinity for P-glycoprotein. This multicenter phase II study assessed the activity of XRP6258 in the treatment of taxane-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: XRP6258 was administered as a 1-h i.v. infusion every 3 weeks at 20 mg/m(2) (then, in the absence of severe toxicity, at 25 mg/m(2) from cycle 2). The primary end point was the objective response rate (ORR) assessed according to response evaluation criteria in solid tumours (RECIST) guidelines. RESULTS: Seventy-one patients were enrolled. The median relative dose intensity was 0.98. The ORR was 14% (two complete, eight partial responses). Eighteen patients (25%) had stable disease of >3 months duration. At a median follow-up of 20.0 months, the median time to progression was 2.7 months, and the median overall survival 12.3 months. The most common grade 3/4 adverse events (AEs) were neutropenia (73%) and leucopenia (55%), with a low febrile neutropenia rate (3%) and infrequent grade 3/4, treatment-related, non-hematological AEs (<5% patients for any AE). Two deaths were reported, one related to study drug and one to unknown cause. CONCLUSIONS: XRP6258 was active and well tolerated in this group of MBC patients with taxane-resistant disease. These results support the further clinical development of this agent