TABLE 2
FROM:
Role of novel targeted therapies in the clinic
R S Herbst
BACK TO ARTICLETable 2. Clinical experience of combination regimens
| Phase of study | Targeted therapy | Chemotherapy | Tumour type/size of study | Status |
|---|---|---|---|---|
| III | Bevacizumab | Irinotecan/5-fluorouracil/leucovorin | Untreated metastatic CRC (n=813) | Complete. The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival (Hurwitz et al, 2004) |
| II | Bevacizumab | Carboplatin/paclitaxel | Advanced/recurrent NSCLC (n=99) | Complete. Inclusion of bevacizumab resulted in a higher response rate compared with the control therapy (31.5 vs 18.8%), a longer median time to progression (7.4 vs 4.2 months) and a trend towards increased survival (17.7 vs 14.9 months) (Johnson et al, 2004) |
| I/II | PTK787 | FOLFOX-4 | Metastatic CRC (n=35) | Complete. Combined treatment was well tolerated at doses  1250 mg day-1; adverse events at 1250 mg day-1 included grade 3 ataxia, thrombocytopenia and dizziness, and grade 4 neutropenia. Grade 3 expressive dysphasia and intermittent dizziness were dose limiting at 1500 mg day-1. Best response data for 28 evaluable patients to date show one CR, 14 PR, and nine stable disease . Estimated median overall survival for 35 patients is 16.6 months (Steward et al, 2004) |
| III | PTK787 | FOLFOX-4 | Metastatic CRC CONFIRM-1 (previously untreated patients): n=>1000 CONFIRM-2 (patients who have progressed after irinotecan-based first-line chemotherapy): n=>800 | CONFIRM-1: analysis of progression-free survival (primary end point) showed no statistically significant improvement over FOLFOX-4 alone (unpublished data). Assessment of overall survival (secondary endpoint) ongoing CONFIRM-2: ongoing |
| III | Bevacizumab | Carboplatin/paclitaxel | Advanced/recurrent NSCLC (first-line) n=878 | Complete. Analysis has demonstrated a survival benefit with bevacizumab/carboplatin/paclitaxel of 12.5 vs 10.2 months with chemotherapy alone (unpublished data) |
| II | ZD6474 | Docetaxel | Locally advanced or metastatic NSCLC after failure of first- line platinum-based chemotherapy n=>200 | Ongoing. Data from safety run-in phase have shown good tolerability with this combination (Heymach et al, 2004b) |
| II | ZD6474 | Carboplatin/paclitaxel | First-line NSCLC (n=>200) | Ongoing. Preliminary data from the safety run-in phase show that the combination is generally well tolerated (Johnson et al, 2005) |
| II | Bevacizumab+erlotinib | Docetaxel (alone or+bevacizumab) | Refractory NSCLC (n=>180) | Ongoing |
| I/II | PTK787 | Temozolomide or lomustine | Glioblastoma multiforme (n=60) | Ongoing. Interim data show good tolerability and promising efficacy (Reardon et al, 2004) |
| I/II | Bevacizumab+erlotinib | n/a | Stage IIIB/IV or recurrent NSCLC (n=40) | Complete. Eight partial responses (20%, CI 7.6-32.4%) and 26 patients with SD (65%, CI 50.2-79.8%). The median survival of 34 patients treated in the phase II part of the study was 12.6 months, with 52% of patients alive at 1 year (Sandler et al, 2004) |
| I | Bevacizumab+BAY 43-9006 | n/a | Various (n=38) | Ongoing |
CR=complete response; SD=stable disease; PR=partial response; NSCLC=non-small-cell lung cancer; CRC=colorectal cancer; n/a=not applicable.
