PMID- 15493356
OWN - NLM
STAT- MEDLINE
DCOM- 20041104
LR  - 20221207
IS  - 0735-7907 (Print)
IS  - 0735-7907 (Linking)
VI  - 22
IP  - 3
DP  - 2004
TI  - Phase I trial of topotecan in combination with gemcitabine in refractory solid 
      tumor patients.
PG  - 360-7
AB  - PURPOSE: To determine maximum tolerated dose (MTD) and evidence of antitumor 
      activity of topotecan in combination with gemcitabine in refractory cancer 
      patients. METHODS: This was a Phase I, prospective, dose-escalation trial that 
      employed a novel-dosing schema to investigate clinical safety. Patients were 
      treated in six cohorts with topotecan (T)+gemcitabine (G). The doses of T and G 
      were administered by 30-minute IV infusion, T on days one through five (0.3 mg/m2 
      to 1 mg/m2) and G on days one and 15 of a 28-day cycle (1000 mg/m2 to 1500 
      mg/m2). Toxicity was monitored. RESULTS: Twenty-three cancer patients were 
      enrolled (colorectal, n=5; lung, n=4; gastric, n=4; esophageal, n=2; other, n=8). 
      Two of three patients developed grade 3 nonhematologic toxicity attributed to 
      study regimen, thereby fulfilling dose limiting toxicity requirements at cohort 6 
      (T, 1 mg/m2, G, 1500 mg/m2). Maximum tolerated dose (MTD) was established at 
      cohort 5 (T, 1 mg/m2, G, 1250 mg/m2). Ten patients were treated at cohort 5. 
      Nonhematologic adverse effects (AEs) >grade 3 attributed to the study regimen 
      were not observed. Hematologic toxicity was frequent. Twenty-five percent of 
      patients in cohort 2 and 50% of patients in cohorts 4, 5, and 6 had a reduction 
      of ANC to <500 mm3. All neutropenic episodes were less than one week in duration. 
      Five of the patients in the last three cohorts required delay and/or 
      dose-reduction of G. Nineteen of 23 enrolled patients were evaluable for 
      response. Two patients achieved a minimal response. CONCLUSIONS: The MTD was 
      observed at a T dose of 1 mg/m2 administered on days 1 through 15, and a G dose 
      of 1250 mg/m2 administered on days 1 and 15 via 30 minute intravenous (IV) 
      infusion.
FAU - Nemunaitis, John
AU  - Nemunaitis J
AD  - US Oncology, Dallas, Texas, USA. john.nemunaitis@usoncology.com
FAU - Cunningham, C Casey
AU  - Cunningham CC
FAU - Vukelja, Suetislava
AU  - Vukelja S
FAU - Ruxer, R L
AU  - Ruxer RL
FAU - Adams, Ned
AU  - Adams N
FAU - Rich, Dawn
AU  - Rich D
FAU - Paulson, A Scott
AU  - Paulson AS
FAU - MacEachern, Jane B
AU  - MacEachern JB
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - Cancer Invest
JT  - Cancer investigation
JID - 8307154
RN  - 0W860991D6 (Deoxycytidine)
RN  - 7M7YKX2N15 (Topotecan)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Cohort Studies
MH  - Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hematologic Diseases/chemically induced
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Prospective Studies
MH  - Topotecan/administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - Gemcitabine
EDAT- 2004/10/21 09:00
MHDA- 2004/11/05 09:00
CRDT- 2004/10/21 09:00
PHST- 2004/10/21 09:00 [pubmed]
PHST- 2004/11/05 09:00 [medline]
PHST- 2004/10/21 09:00 [entrez]
AID - 10.1081/cnv-200029060 [doi]
PST - ppublish
SO  - Cancer Invest. 2004;22(3):360-7. doi: 10.1081/cnv-200029060.