Spectrum of antitumor activity for PD 0322991 against a panel of advanced stage human tumor xenografts
| Tumor* | Dose (mg/kg),† MTD‡ or highest dose tested | Dosing schedule | % Weight change§ | T-C∥ | Net log10 kill¶ |
|---|---|---|---|---|---|
| Colo-205 colon | 150‡ | Days 18–31 | −6 | 48.4 | +1.20 |
| MDA-MB-435 breast | 150‡ | 12–39 | + | 32.7 | +0.25 |
| SF-295 glioblastoma | 150‡ | 7–20 | −11 | 30.1 | +2.24 |
| ZR-75-1 breast | 150‡ | 7–20 | −4 | 12.4 | −0.06 |
| PC-3 prostate | 130 | 8–21 | −13 | 12.8 | +0.02 |
| H125 lung | 150‡ | 19–32 | −12 | 7.3 | −0.31 |
| SW-620 colon | 150‡ | 10–23 | −3 | 5.9 | −0.55 |
| H23 lung | 130 | 9–22 | + | 4.8 | −1.07 |
| MDA-MB-468 breast (Rb negative) | 150‡ | 22–35 | −2 | −4.3 | — |
↵* All tumors are Rb positive, except MDA-MB-468 in which Rb is deleted.
↵† The vehicle was 50 mmol/L lactate buffer at pH 4.0. PD 0332991 was given daily p.o. for 14 days, except for MDA-MB-435, which was given for 28 days. Treatments were started when the tumor weights were between 100 and 150 mg.
↵‡ MTD, maximum tolerated dose.
↵§ A negative number is the percentage weight loss seen during treatment. A plus indicates a weight gain through treatment.
↵∥ T-C is the difference (in days) for the treated and control tumors to reach an evaluation size of 750 mg. A T-C of 0 would indicate no effect.
↵¶ Net log10 tumor cell kill represents the change in tumor burden during therapy. A negative value indicates a net increase in tumor mass during therapy, whereas a positive value indicates a net reduction in tumor burden. Values near 0 indicate tumor stasis during therapy.