No abstract

FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.

No abstract

Patients with peripheral T-cell lymphomas (PTLs) have an extremely poor prognosis when relapsed or refractory to conventional chemotherapy. We have studied alemtuzumab, a humanized anti-CD52 monoclonal antibody, as therapy for patients with heavily pretreated and refractory PTL. Fourteen patients entered the study. All had clinical stage III or IV disease. Patients received a rapidly escalating dosage of alemtuzumab during the first week and, thereafter, 30 mg intravenously 3 times per week for a maximum of 12 weeks. Trimethoprim/sulphamethoxazole and valaciclovir prophylaxis was given to all patients. The overall response rate was 36% (5 of 14). Three patients achieved a complete remission (CR) and 2 patients a partial remission. The durations of the CRs were 2, 6, and 12 months, respectively. Toxicity included cytomegalovirus reactivation in 6 patients, which was successfully treated with ganciclovir or foscarnet; pulmonary aspergillosis in 2 patients; and pancytopenia in 4 patients. Epstein-Barr virus-related hemophagocytosis was observed in 2 patients. Five patients died of causes related to the treatment, in combination with advanced disease. We conclude that alemtuzumab is active when used in patients with advanced, heavily pretreated PTL, although it is associated with significant hematologic toxicity and infectious complications. Further studies are warranted in younger patients and patients with less advanced disease. (Blood. 2004;103: 2920-2924)

Biweekly FLOT is active and has a favorable safety profile.

Background: FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined. Patients and Methods: In this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method. Results: CMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n ¼ 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%). CMS distribution in right-versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment, CMS was a strong prognostic factor for ORR (P ¼ 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy. Conclusions: CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making. The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.

Biweekly fluorouracil, folinic acid, and oxaliplatin is active and well-tolerated in patients with advanced gastric cancer. Response rates, time to progression, and overall survival were comparable to those achieved with other combination chemotherapy regimens, including FOLFOX6, with significantly less toxicity.

Our data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti-epidermal growth factor receptor-directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents.