Completed trials at CWRU using sequential CT-guided biopsies of solid tumors for Phase I/II drug development
| Study . | No. ptsa on trial (requiring biopsy) . | No. pts having biopsies . | No. of biopsies . | Location of biopsies . | Primary tumor . | Pharmacodynamic end point . | Success rate for obtaining paired biopsies containing tumor . |
|---|---|---|---|---|---|---|---|
| Phase I trial of tiazofurin and BCNU (Ref. 6) | 21 (ns) | 10 | 18 | Liver 4 LN 4 Abdo wall 1 Subcut 1 | Colorectal 8 Melanoma 1 SCLC 1 | Depletion 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) | 8 | 8 (pretreatment only) | Liver 4 LN 3 Pelvic mass 1 | Colorectal 8 | No 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) | 10 | 19 | Liver 9 LN 1 | Colon 10 | Streptozotocin decreased alkyltransferase levels but incompletely. | 9 of 10 1 vasovagal reaction |
| Phase I trial of O6BG and BCNU (Ref. 3) | 53 (38 requiring biopsy) | 38 | 62 | Liver 28 Breast 3 LN 2 Lung 1 Abd. mass 2 Cheat wall 1 Spleen 1 | Breast 5 Colorectal 22 Lungs 2 Renal 1 Gastric 3 Sinus 1 UNK pr. 2 Pancreas 1 Soft tissue sarcoma 1 | Increasing 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) | 16 | 31 | Liver 15 LN 1 | Colorectal 8 Sinus 1 Pancreas 2 Melanoma 1 Small int 1 Breast 2 Unk pr 1 | Temozolamide 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) | 4 | 12 (3 each) | H + N Cancer 4 | H + N Cancer 4 | Correlation 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) | 21 | 42 | Liver 18 Pelvic mass 2 LN 1 | Colon 21 | Determination of topoisomerase levels as predictors of response to irinotecan. Results pending. | 21 of 21 |
| Total | — | 107 | 192 | Liver 78 LN 12 Pelvic/abdo mass 5 H + N 4 Breast 3 Chest/abdo wall 2 s.c. 1 Splenic 1 Lung 1 | Colorectal 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) |
| Study . | No. ptsa on trial (requiring biopsy) . | No. pts having biopsies . | No. of biopsies . | Location of biopsies . | Primary tumor . | Pharmacodynamic end point . | Success rate for obtaining paired biopsies containing tumor . |
|---|---|---|---|---|---|---|---|
| Phase I trial of tiazofurin and BCNU (Ref. 6) | 21 (ns) | 10 | 18 | Liver 4 LN 4 Abdo wall 1 Subcut 1 | Colorectal 8 Melanoma 1 SCLC 1 | Depletion 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) | 8 | 8 (pretreatment only) | Liver 4 LN 3 Pelvic mass 1 | Colorectal 8 | No 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) | 10 | 19 | Liver 9 LN 1 | Colon 10 | Streptozotocin decreased alkyltransferase levels but incompletely. | 9 of 10 1 vasovagal reaction |
| Phase I trial of O6BG and BCNU (Ref. 3) | 53 (38 requiring biopsy) | 38 | 62 | Liver 28 Breast 3 LN 2 Lung 1 Abd. mass 2 Cheat wall 1 Spleen 1 | Breast 5 Colorectal 22 Lungs 2 Renal 1 Gastric 3 Sinus 1 UNK pr. 2 Pancreas 1 Soft tissue sarcoma 1 | Increasing 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) | 16 | 31 | Liver 15 LN 1 | Colorectal 8 Sinus 1 Pancreas 2 Melanoma 1 Small int 1 Breast 2 Unk pr 1 | Temozolamide 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) | 4 | 12 (3 each) | H + N Cancer 4 | H + N Cancer 4 | Correlation 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) | 21 | 42 | Liver 18 Pelvic mass 2 LN 1 | Colon 21 | Determination of topoisomerase levels as predictors of response to irinotecan. Results pending. | 21 of 21 |
| Total | — | 107 | 192 | Liver 78 LN 12 Pelvic/abdo mass 5 H + N 4 Breast 3 Chest/abdo wall 2 s.c. 1 Splenic 1 Lung 1 | Colorectal 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) |
Pt, patient; ns, not stated in protocol; SCLC, small cell lung cancer.