Table 3.

Spectrum of antitumor activity for PD 0322991 against a panel of advanced stage human tumor xenografts

Tumor*Dose (mg/kg), MTD or highest dose testedDosing schedule% Weight change§T-CNet log10 kill
Colo-205 colon150Days 18–31−648.4+1.20
MDA-MB-435 breast15012–39+32.7+0.25
SF-295 glioblastoma1507–20−1130.1+2.24
ZR-75-1 breast1507–20−412.4−0.06
PC-3 prostate1308–21−1312.8+0.02
H125 lung15019–32−127.3−0.31
SW-620 colon15010–23−35.9−0.55
H23 lung1309–22+4.8−1.07
MDA-MB-468 breast (Rb negative)15022–35−2−4.3
  • * 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.