World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website http://www.wjon.org

Review

Volume 6, Number 5, October 2015, pages 429-436


Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature

Tables

Table 1. Phase I Clinical Trials of Topotecan as Combination Therapy
 
Author and yearPhasePatientsnDrugs and dosageDisease responseMedian survival
PR: partial remission; SD: stable disease; n: number of patients.
Raymond et al, 1997 [14]IUntreated advanced NSCLC14TPT (0.75 mg/m2/day) as 30 min infusion daily for 5 days with cisplatin given at 75 mg/m2 on day 1 every 3 weeks4 (30.7%) had PRTumor response lasted for 12 weeks
Rinaldi et al, 2001 [15]I/IIPreviously treated advanced NSCLC19TPT (0.75 mg/m2/day) as 30 min infusion daily for 5 days and gemcitabine 400 mg/m2 on days 1 and 5 only3 (18%) had PR, 6 (32%) had SD10 months
Stupp et al, 2001 [16]I/IIRecurrent or metastatic NSCLC29IV TPT (0.5 - 1 mg/m2/day) for 5 days and IV vinorelbine (20 - 30 mg/m2/day) on days 1 and 5 only every 21 days42% clinical response rate13 months
Guarino et al, 2002 [17]IUntreated stage IIIb/IV NSCLC30IV TPT (1.75 mg/m2), cisplatin (20 mg/m2) on days 1, 8, and 15 and gemcitabine (1,000 mg/m2) on days 1 and 15 of a 28-day cycle11 (38%) had PR38 weeks. One-year survival rate was 33%.
Dabrow et al, 2003 [18]I/IIUntreated stage IIIb/IV NSCLC24IV TPT (2 mg/m2) and gemcitabine (1,250 mg/m2) on days 1, 8, and 15 of a 28-day cycle5 (21%) had PR22 weeks
Beldner et al, 2007 [19]IPreviously treated advanced NSCLC18IV vinorelbine (20 mg/m2) and TPT (2 - 4 mg/m2) on days 1 and 8 every 21 days1 had PR, 4 (27%) had SD10.5 months

 

Table 2. Phase II Clinical Trials of Topotecan as Single-Agent Therapy
 
Author and yearPhasePatientsnDose of topotecanDisease responseMedian survival
SD: stable disease; PR: partial remission; PRG: progression of disease; SCC: squamous cell cancer, n: number of patients.
Lynch et al, 1994 [6]IIUntreated advanced NSCLC202 mg/m2/day IV for 5 days every 21 days for two cycles11 (55%) had SD, 9 (45%) had PRG.7.6 months
Perez-Soler et al, 1996 [7]IIUntreated advanced NSCLC401.5 mg/m2/day for 5 days every 21 days6 (15%) had PR, 10 had SD and 20 had PRG. 36% PR in patients with SCC.38 weeks and 30% patients were alive at 1 year
Mainwaring et al, 1997 [9]IIUntreated advanced NSCLC120.6 mg/m2/day as continuous IV infusion for 21 days every 4 weeks1 (8%) had PR.Not reached
Kindler et al, 1998 [10]IIUntreated advanced NSCLC260.6 mg/m2/day as continuous IV infusion for 21 days every 4 weeks1 (4%) had PR.9 months and 1-year survival was 39%.
Weitz et al, 2000 [8]IIUntreated advanced NSCLC381.5 mg/m2/day over 30min for 5 days every 21 days6 (16%) had PR.257 days (37 weeks)
Weitz et al, 2000 [8]IIUntreated advanced NSCLC371.3 mg/m2/day as continuous infusion over 72 h every 21 days3 (8%) had PR.179 days (26 weeks)
White et al, 2000 [11]IIUntreated advanced NSCLC292.3 mg/m2/day orally for 5 days every 21 days for up to six cycles13 (43.3%) had SD. No PR. 3 had radiological response.39.9 weeks and 1-year survival of 33.3%
Gonzalez et al, 2011 [20]IIAdvanced NSCLC pre treated with platinum and taxanes351.25 mg/m2/day IV daily for 5 days every 21 days for 73 cycles1 (2.8%) had PR, 9 (25.7%) had SD, 23 (65.7%) had PRG.70 days

 

Table 3. Phase II Clinical Trials of Topotecan as Combination Therapy
 
Author and yearPhasePatientsnDrugs and dosageDisease responseMedian survival
RCT: randomized controlled trial; ORR: overall response rate; MR: minimal remission; PFS: progression-free survival.
Dowlati et al, 2001 [21]IIUntreated advanced NSCLC19TPT at 0.85 mg/m2/day as a continuous 72-h infusion from days 1 to 3 and etoposide at 100 mg PO twice daily for 3 days on days 7 - 9. Total of 55 cycles.1 PR and 2 SDOne-year survival rate was 33%.
Joppert et al, 2003 [22]IIUntreated advanced NSCLC51TPT 1 mg/m2 on days 1 - 5, and gemcitabine 1 g/m2 on days 1 and 15 IV, every 28 days.8 (17%) had PR, 11 (23%) had SD7.6 months. One-year survival rate was 39%.
Lorusso et al, 2005 [23]IIPreviously treated advanced NSCLC42TPT (1.2 mg/m2) plus ifosfamide (1,200 mg/m2) IV for three consecutive days every 3 weeks. Total of three cycles.6 (14.2%) had PR, 1 (2.4%) had MR, 14 (34%) had SD, 21 (51%) had PRG26 weeks. One-year survival rate was 14%.
Stathopoulos et al, 2006 [24]IIUntreated advanced NSCLC45TPT (1.75 mg/m2) infused over 30 min and paclitaxel (70 mg/m2) infused over 90 min, weekly for 3 weeks every 28 days up to three cycles.2 (4.4%) had CR, 16 (35.6%) had PR, 21 (46.7%) had SD, 6 (13.3%) had PRG9 months
Jones et al, 2008 [25]II. RCTPreviously treated advanced NSCLC8039 received TPT (2 or 2.5 mg/day, for 5 of 7 days for 2 weeks) orally and 41 received docetaxel (75 mg/m2) every 21 days.8% ORR with TPT and docetaxel8.4 months with TPT and 7.6 months with docetaxel
Powell et al, 2013 [26]IIPreviously treated advanced NSCLC42TPT (4 mg/m2) on days 1, 8, and 15 and bevacizumab (10 mg/kg) on days 1 and 15 as IV infusion every 28 days.14.3% had PR, 54.8% had SD, 28.6% had PRGPFS was 5.1 months and overall survival was 11.5 months.