Phase I and pharmacokinetic study of the combination of topotecan and ifosfamide administered intravenously every 3 weeks.

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of topotecan administered as a 30-min intravenous (i.v.) infusion over 5 days in combination with a 1-h i.v. infusion of ifosfamide (IF) for 3 consecutive days every 3 weeks. Patients with advanced malignancies refractory to standard therapy were entered into the study. The starting dose of topotecan was 0.4 mg x m(-2) day(-1) x 5 days. Ifosfamide was administered at a fixed dose of 1.2 g x m(-2) day(-1) x 3 days. In all, 36 patients received 144 treatment courses. Owing to toxicities, the schedule of topotecan administration was reduced from 5 to 3 days. The MTD was reached at topotecan 1.2 mg x m(-2) day(-1) x 3 days with IF 1.2 g x m(-2) day(-1) x 3 days. Haematological toxicities were dose limiting. Neutropenia was the major toxicity. Thrombocytopenia and anaemia were rare. Nonhaematological toxicities were relatively mild. Partial responses were documented in three patients with ovarian cancer dosed below the MTD. Topotecan and IF did not appear to interact pharmacokinetically. The relationships between the exposure to topotecan lactone and total topotecan, and the decrease in absolute neutrophil count and the decrease in thrombocytes, were described with sigmoidal-E(max) models. The combination of 1.0 mg m(-2) day(-1) topotecan administered as a 30-min i.v. infusion daily times three with 1.2 g x m(-2) day(-1) IF administered as a 1-h i.v. infusion daily times three every 3 weeks was feasible. However, the combination schedule of topotecan and IF did result in considerable haematological toxicity and in conjunction with previously reported pronounced nonhaematological toxicities and treatment related deaths, it may be concluded that this is not a favourable combination.

Nursing in Colorectal Cancer Initiative: the audit phase. Part 2. Content validity of the audit tool and implications of the standards set for clinical practice.

This paper gives an account of the process of refining the content validity of an audit tool, which defines and measures best practice in colorectal cancer nursing and identifies areas for development. The European Oncology Nursing Society (EONS) and AstraZeneca collaborated to develop the Nursing in Colorectal Cancer Initiative (NICCI). The initiative was funded through educational grants from AstraZeneca and led by EONS. It is a project with two components, education and audit. The education component culminated in a manual that provides a core set of materials concerning fundamental aspects of colorectal cancer, to foster a common understanding amongst nurses at national and international levels. An audit tool was developed to measure standards of nursing care in relation to the delivery of cytotoxic chemotherapy to patients with advanced colorectal cancer. The content validity of the audit tool was established in three stages by expert panel review with revisions made to the content and organisation of the audit measures at each stage. The standards set by the NICCI Audit Project have key implications for multi-professional practice in colorectal cancer care.

Nursing in Colorectal Cancer Initiative--the audit phase. Part 1. Development of the audit tool.

This paper describes the structure of an audit study together with the two-phase development of an audit tool and methodology. The purpose of the study was to develop a tool that defines and measures best practice in colorectal cancer nursing, and identifies areas for development. The European Oncology Nursing Society (EONS) and AstraZeneca collaborated to develop the Nursing in Colorectal Cancer Initiative (NICCI). The initiative was funded through educational grants from AstraZeneca and led by EONS. It is a project with two components, education and audit. The purpose of the project is to provide a sound educational basis for nurses in the elements of colorectal cancer care, together with the tools to evaluate and develop practice. The education phase culminated in an educational manual that provides a core set of materials concerning the fundamental aspects of colorectal cancer, to foster a common understanding amongst nurses nationally and internationally. The education manual provided the referenced rationale for the definition of a set of hallmarks and standards of clinical practice. The audit tool was developed from the hallmarks and standards and is focused on the care of patients receiving cytotoxic chemotherapy for colorectal cancer. The audit methodology is based on the structure, process outcome triad, together with the TELER system of audit.