Table 5.
Clinical trials of lurtotecan (GI147211/GI-147211, NX211/NX-211, OSI211/OSI-211)
| Key | Route & dose | Formulation | Cancer type and key clinical trial outcome | Refs |
|---|---|---|---|---|
| 1996 Phase I | 0.5 h iv d1-5 at 0.3-1.5 mg/m2/d; 3 wk/c: ≥ 3/pt | Drug diluted w D5W | 18 pts w refractory solid tumors; DLT: NP, TCP; PR: 1 pt; Phase II: 1.2 mg/m2 on d1-5, 3 wk/c | No 1 [244] |
| 1998 Phase I | 0.5 h iv d1-5 at 0.3-1.75 mg/m2/d; 3 wk/c: ~3/pt | Drug diluted in 5% dextrose in water (D5W) | 24 pts w advanced solid tumors; DLT: NP, TCP; Phase II: 1.0 mg/m2 on d1-5, 3 wk/c; manageable toxicity but need to see distinct efficacy | No 2 [245] |
| 1998 Phase I | 72 h iv at 0.25-2.5 mg/m2/d | Drug diluted in D5W | 44 pts w advanced solid tumors; DLT: NP, TCP; PR: 3 pts; Phase II: 1.75 (MP), 1.2 (HP) mg/m2/d | No 3 [246] |
| 2000 Phase II | 0.5 h iv d1-5 at 1.2 mg/m2/d; 3 wk/c: ≥ 2/pt (267 c/67 pts) | Drug diluted 5% dextrose in water (D5W) | 67 pts w breast/NSCLC/colon tumors; DLT: NP, TCP, anemia; PR: 3/25 (breast), 2/23 (NSCLC), 0/19 (colon); conclusion: modest activity. | No 4 [247] |
| 2000 Phase II | 0.5 h iv d1-5 at 1.2 mg/m2/d; 3 wk/c: ≥ 2/pt - ≤ 4/pt | Drug diluted 5% dextrose in water (D5W) | pts w refractory (28) & chemosensitive (34) SCLC; ORR: 16.6%; PR: observed; DLT: NP (25%), TCP (23%). Conclusion: antitumor efficacy and toxicity is equivalent to topotecan. | No 5 [248] |
| 2002 Phase I | 0.5 h iv at 0.4, 0.8, 1.6, 3.8, 4.3 mg/m2; 3 wk/c: ≥ 2/pt (77 c/29 pts) | Liposomal form w 10 mM NH4Cl 9% sucrose | 29 pts w solid tumors; DLT: NP, TCP; antitumor activity unclear; Phase II dose: 3.8 mg/m3 once every 3 weeks (3 wk/c) | No 6 [249] |
| 2002 Phase II | 0.5 h iv d1-5 at 1.2 mg/m2/d; 3 wk/c: ≥ 2/pt | Drug diluted 5% dextrose in water (D5W) | 173 pts w solid tumors (breast, colon, N/SCLC, ovarian); DLT: myelosuppression; antitumor activity unclear; PK focused. | No 7 [250] |
| 2004 Phase II | 0.5 h iv d1, d8 at 2.4 mg/m2/d; 3 wk/c: ≥ 2/pt | Liposomal form | 46 pts w head & neck squamous cell carcinoma; ORR: 1 pt & SD: 18 pts (18 wk); grade 1/2 anemia in 79%, but minimal antitumor activity | No 8 [251] |
| 2004 Phase I | 0.5 h iv d1-3 at 0.15-2.1 mg/m2/d; 3 wk/c* | Liposomal form | 37 pts w solid tumors; DLT: myelosuppression; MTD: 2.1 (MP), 1.8 (HP) mg/m2/d; PR: 2 pts; | No 9 [252] |
| 2004 Phase I | 0.5 h iv d1-3 at ≥ 1.5 mg/m2/d; 3 wk/c* | Liposomal form | 20 pts w leukemia; DLT: mucositis, diarrhea; MTD: 3.7 mg/m2/d; minimal activity | No 10 [253] |
| 2004 Phase I | iv d1-3 at 0.9 (Cis: 25) mg/m2/d; 3 wk/c | Liposomal form | 14 pts w solid tumors; DLT: NP, TCP; Phase II: 0.7 + 25 (Cis) mg/m2/d; CR: 1 pt; PR: 3 pts | No 11 [254] |
| 2004 Phase II | 0.5 h iv d1, d8 at 2.4 mg/m2/d; 3 wk/c | Liposomal form in D5W | 22 pts w topotecan-resistant ovarian cancer; highly manageable toxicity; no evidence of clinical activity (only 8 pts w SD) | No 12 [255] |
| 2005 Phase II/IIIa | 0.5 h iv d1-3 at 1.8 (arm A) or on d1, d8 (arm B) mg/m2/d; 3 wk/c*: ≥ 2/pt | Liposomal form w 10 mM NH4Cl 9% sucrose | 80 pts w relapse ovarian cancer; hematologic toxicity: arm A (51%) > arm B (22%); ORR: 10% (A: 15.1% vs. B:4.9%) | No 13 [256] |