Genta Inc. demnächst mit neuen Studienergebnissen
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Eröffnet am: | 28.04.11 12:57 | von: raurunter | Anzahl Beiträge: | 265 |
Neuester Beitrag: | 21.03.12 19:19 | von: steven-bln | Leser gesamt: | 23.114 |
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veröffetlicht werden.
Bisher hat Genta kaum Erfolge zu bieten und so sieht auch der Kurs aus.
Sollte es diesmal gelingen und eine Trendwende auslösen?
Background: Tesetaxel, a novel oral taxane, yielded a 20% major objective response rate in pretreated patients (pts) with advanced gastric cancer when administered at a dose of 27 mg/m2 Q3 wks. Relative to docetaxel, tesetaxel is not a substrate for P-gp, is associated with lower neurotoxicity, and does not cause hypersensitivity or require premedications. We have conducted a dose-ranging study of tesetaxel to determine whether “flat” (rather than weight-based) dosing of this new agent would be feasible for phase III testing. Methods: Pts with advanced gastric cancer who had failed 1 prior fluoropyrimidine/cisplatin regimen were accrued to 1 of 3 cohorts. Tesetaxel was administered to pts in Cohorts 1 and 2 once every 3 weeks at a flat starting dose of 40-45 mg and 50-60 mg, respectively. In Cohort 3, the starting dose was 27 mg/m2. For analysis, flat doses were converted to weight-based (body-surface area [BSA]) equivalents. Standard parameters of response and safety were compared. Results: Tesetaxel was well tolerated. No episodes of ≥ grade 3 neutropenia occurred in either flat-dose cohort. We found substantial BSA variability in both flat-dose cohorts (median BSA = 1.9 and 2.0 mg/m2, respectively), which resulted in substantial underdosing compared with the weight-based regimen. Weight-based doses as low as 19 and 20 mg/m2, respectively, were administered in the 2 flat-dose cohorts. Among 11 evaluable pts in Cohort 1, the lower flat-dose regimen yielded 1 unconfirmed partial response (uPR) and 1 stable disease (SD). Among 13 evaluable pts in Cohort 2, the higher flat-dose regimen yielded 1 uPR and 4 SD; it is too early to evaluate 3 pts. Pts are currently being accrued to the weight-based regimen. Conclusions: On the Q3 week schedule, flat dosing of tesetaxel results in substantial underdosing of pts due to high BSA variability in Western subjects. Safety and response to tesetaxel in pts with advanced gastric cancer appear to be dose-related. A randomized Phase 3 study will proceed using the Q3 week schedule supported in this trial. Our data suggest a starting dose of 27 mg/m2, with escalation to 35 mg/m2 depending on tolerance, appears optimal.
Background: Oblimersen (OBL) is a Bcl-2 targeted phosphorothioate antisense that enhances antitumor activity of alkylating agents in preclinical studies. A prior phase III study of dacarbazine + OBL in 771 patients (pts) showed significant improvement in all secondary endpoints, including overall response and progression-free survival (PFS), in pts treated with OBL/DTIC, but that the primary endpoint of ITT overall survival (OS) was narrowly missed (P=0.077). Further analysis showed that OS benefit from OBL plus DTIC clustered in pts with low-normal LDH, who displayed a significant treatment interaction with this adverse prognostic factor. We have completed a similarly designed trial (AGENDA) to evaluate whether addition of OBL to DTIC could confirm the OS benefit previously observed in pts with low-normal LDH. Methods: Inclusion criteria included: unresectable Stage 3 or 4 melanoma; no prior chemotherapy; LDH ≤ 0.8 x ULN; ECOG PS 0-1. Pts were randomized to receive DTIC (1000 mg/m2 IV) preceded by a 5-day continuous IV infusion of either OBL (7 mg/kg/d) or placebo. Up to 8 cycles were administered absent progressive disease. Co-primary endpoints of progression-free survival (PFS) and OS were to be analyzed 6 months and 2 years after last patient was accrued, respectively. The trial was powered to detect an increase in OS (HR=0.69; a = 0.05). Results: Accrual completed in March 2009 with 314 patients. Treatment groups were balanced with respect to baseline characteristics. LDH was poorly correlated with tumor burden (R=0.16). As previously reported, PFS favored the DTIC-OBL regimen but was not significant (HR=0.85; P=0.23). The protocol allowed for “pooling” of survival data between the 2 studies. An exploratory analysis revealed a modest improvement in pooled PFS data (HR=0.71; P=0.0004). The single primary analysis for OS (and the secondary endpoint of durable response) will be conducted in April 2011. Conclusions: Results for the co-primary AGENDA endpoint of OS will be presented.
Ich finde jetzt ist es an der Zeit wieder mal Gewinne zu machen und wenn alle verkaufen werde ich zukaufen so geht es immer.
Frei nach der Devise: Wer zu spät oder zu früh kommt der ist der Verlierer und wer nicht wagt der nicht gewinnt.
Worauf soll ich denn sonst noch warte. Billiger wird es nimmer.