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Biomedical subjects

Graham Ross

Publications and source records attributed to Graham Ross.

5 recordsLinked to original sources
PubMed2006

Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer.

PURPOSE: This open-label, randomized, multicenter, phase III study compared oral topotecan versus intravenous (IV) docetaxel in patients with previously treated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage III or IV NSCLC, performance status < or = 2, who had received only one prior chemotherapy regimen, were randomly assigned to treatment with oral topotecan 2.3 mg/m2/d on days 1 to 5 or IV docetaxel 75 mg/m2 day 1 every 21 days. RESULTS: A total of 829 patients were randomly assigned. In intent-to-treat analysis, 1-year survival rates were 25.1% with topotecan and 28.7% with docetaxel. The difference of -3.6% (95% CI, -9.59% to 2.48%) met the predefined criteria for noninferiority of topotecan relative to docetaxel because the lower limit of the 95% CI was above -10%. Median survival was 27.9 weeks with topotecan and 30.7 weeks with docetaxel. Although not statistically significant (log-rank P = .057), the higher survival rate with docetaxel was maintained across the entire treatment period. The median time to progression was 11.3 weeks with topotecan versus 13.1 weeks with docetaxel (log-rank P = .02). The overall response rate was 5% in each group. Grade 3/4 neutropenia occurred more frequently with docetaxel (60% v 50%). Grade 3/4 anemia and thrombocytopenia occurred more frequently with topotecan (26% v 10% and 26% v 7%, respectively). CONCLUSION: Oral topotecan provides activity in the treatment of relapsed, locally advanced, unresectable NSCLC. Both regimens were well tolerated with differing safety profiles. Topotecan may provide an option for patients who desire an orally available treatment after relapse.

Administration, Oral↗
PubMed2006

Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer.

PURPOSE: This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 (n = 389) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 (n = 395) every 21 days. RESULTS: Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of -0.03 (95% CI, -6.53 to 6.47) met the predefined criteria of < or = 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance. CONCLUSION: Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.

Administration, Oral↗
PubMed2005

A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer.

PURPOSE: Topotecan (Hycamtin is active in small-cell lung cancer (SCLC). This phase II study investigated the efficacy and safety of topotecan in combination with either cisplatin or etoposide in untreated extensive disease SCLC (ED SCLC). PATIENTS AND METHODS: Patients with untreated ED SCLC were randomised to treatment with T/C (topotecan 1.25mg/(m(2)day) IV days 1-5, cisplatin 50mg/m(2) IV day 5; 41 patients) or T/E (topotecan 0.75 mg/(m(2)day) IV days 1-- 5, etoposide 60 mg/(m(2)day) IV days 1-5; 41 patients) every 21 days. Response was evaluated by strict radiological criteria. RESULTS: Response rates were similar for T/C (63.4%, 95% CI: 48.7-78.2%) and T/E (61.0%, 95% CI: 46-76%) with one patient in each arm who underwent complete response. Median survival was 41.6 weeks (9.6 months) for the T/C group and 43.7 weeks (10.1 months) for the T/E group. Toxicity was primarily haematological in both groups. The proportion of patients with grades 3-4 anaemia was significantly higher in the T/C arm (46.4%) versus 20% with the T/E arm (p=0.018). The proportion of patients with grade 4 neutropenia was not significantly lower with T/C (56.1%) than with T/E (65.0%, p=0.41), as was the incidence of associated events such as sepsis (T/C: 0%; T/E: 9.8%, p=0.11). The overall deliverability of either regimen was similar. The most frequent non-haematological adverse experiences of all grades per patient were nausea (T/C: 43.9%; T/E: 36.6%), and alopecia (T/C: 39.0%; T/E: 56.1%). Topotecan did not appear to increase the frequency of adverse events specifically associated with cisplatin. CONCLUSION: This study showed T/C and T/E to be effective and well tolerated in patients with ED SCLC and further evaluation of topotecan in first line SCLC is warranted.

Adult↗
PubMed2002

Population pharmacokinetic and adverse event analysis of topotecan in patients with solid tumors.

OBJECTIVE: Our objective was to describe the pharmacokinetics and pharmacodynamics of topotecan in patients. METHODS: Data were pooled from 9 clinical trials. Topotecan, as a single-agent therapy, was administered as a daily 30-minute intravenous infusion for 5 days on a 3-week cycle. Doses of 0.2 to 2.0 mg/m(2) were studied; concentration and neutropenic event data were obtained on multiple occasions. The pharmacokinetics were characterized with use of hierarchical nonlinear regression. The relationship between severity of neutropenia and exposure was characterized with use of logistic regression. RESULTS: The pharmacokinetics of topotecan were described with a linear 2-compartment model. Compromised renal function, low body weight, and poor Eastern Cooperative Oncology Group performance status were determinants of lower clearance, resulting in elevated exposure. Application of covariates reduced interpatient variability in clearance. Logistic regression showed that topotecan area under the concentration-time curve from 0 to 24 hours was predictive of the severity of neutropenia; the only other significant covariate was the number of courses of previous treatment with platinum-based regimens. CONCLUSIONS: Patients with compromised renal function, low body weight, or poor performance status had low topotecan clearance. Patients with high topotecan AUC had an increased probability of experiencing severe neutropenia, which was greater if the patient had been pretreated with platinum-based agents. The use of covariates to individualize dose would result in less variability in exposure, reducing the likelihood of severe neutropenia and potentially improving treatment benefit.

Adult↗