Table 1

Completed trials at CWRU using sequential CT-guided biopsies of solid tumors for Phase I/II drug development

StudyNo. ptsa on trial (requiring biopsy)No. pts having biopsiesNo. of biopsiesLocation of biopsiesPrimary tumorPharmacodynamic end pointSuccess rate for obtaining paired biopsies containing tumor
Phase I trial of tiazofurin and BCNU (Ref. 6)21 (ns)1018Liver 4 LN 4 Abdo wall 1 Subcut 1Colorectal 8 Melanoma 1 SCLC 1Depletion of nicotinamide and ATP with tiazofurin. No correlation was seen.   7 of 103 pts with either normal or necrotic tissue on one of the two biopsies
Phase I trial of topotecan as 72-h weekly infusion (Ref. 8)22 (ns)88 (pretreatment only)Liver 4 LN 3 Pelvic mass 1Colorectal 8No correlation between pretreatment topoisomerase levels and response was seen.   6 of 82 fibrotic specimens
Phase I trial of streptozotocin and BCNU (Ref. 7)15 (10 requiring biopsy)1019Liver 9 LN 1Colon 10Streptozotocin decreased alkyltransferase levels but incompletely.   9 of 10 1 vasovagal reaction
Phase I trial of O6BG and BCNU (Ref. 3)53 (38 requiring biopsy)3862Liver 28 Breast 3 LN 2 Lung 1 Abd. mass 2 Cheat wall 1 Spleen 1Breast 5 Colorectal 22 Lungs 2 Renal 1 Gastric 3 Sinus 1 UNK pr. 2 Pancreas 1 Soft tissue sarcoma 1Increasing doses of O6-benzylguanine resulted in total depletion of alkyltransferase.  31 of 38 5 necrotic tissue 1 caps hemorrhage 1 pt refused second biopsy
Phase I trial of temozolomide (Ref. 4)22 (16 requiring biopsy)1631Liver 15 LN 1Colorectal 8 Sinus 1 Pancreas 2 Melanoma 1 Small int 1 Breast 2 Unk pr 1Temozolamide depletion of alkyltransferase was demonstrated but with residual alkyltransferase activity.  15 of 16 1 pt refused second biopsy
Phase I trial of paclitaxel and concurrent radiation in head and neck cancer (Ref. 5)24 (ns)412 (3 each)H + N Cancer 4H + N Cancer 4Correlation of paclitaxel dose and mitotic arrest was seen.   4 of 4
Phase II trial of irinotecan in colon cancer (Ref. 9)21 (all require biopsy)2142Liver 18 Pelvic mass 2 LN 1Colon 21Determination of topoisomerase levels as predictors of response to irinotecan. Results pending.  21 of 21
Total107192Liver 78 LN 12 Pelvic/abdo mass 5 H + N 4 Breast 3 Chest/abdo wall 2 s.c. 1 Splenic 1 Lung 1Colorectal 77 Breast 7 H + N 4 Pancreas 3 Unknown primary 3 Gastric 3 Melanoma 2 Lung 2 Sinus 2 Renal 1 SCLC 1 Small intestinal 1 Soft tissue sarcoma 1  87 of 99    (88%) (excluding the 8 pts who were planned to receive pretreatment biopsy only)
  • a Pt, patient; ns, not stated in protocol; SCLC, small cell lung cancer.