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Performance status has shown to be a major negative prognostic factor in lung cancer. Because of the limited time expectancy of these patients, individual clinical benefit (Koeberle) of any intervention should be the main focus. This contrasts the mainly pharmaceutical industry driven studies which traditionally focused on tumour response rates, progression free and overall survival neglecting patient-derived experiences. As secondary objective of registration trials in oncology frequently so called “quality-of-life” (QoL) outcomes are reported. Herein however, commonly a composite of both cancer-related symptoms and anti-cancer treatment-related toxicities are included. First line, platinum based chemotherapy doublets are associated with increased toxicity and toxic death rates in patients with a PS of 2 (Zukin), indicating, that a more prudent dosing in this vulnerable population is warranted. The benefit of chemotherapy in PS 3 patients continues to be speculative although a number of these patients are actually receiving chemotherapy in many institutions including our own, often with initial dose reductions in an empiric manner (Salloum). Minimal published data are available on such patients (characteristics of clinical benefit responders and non-responders). In the light of both criticism of chemotherapy in PS 3 patients and encouragement to not neglect them there is a current demand for research (Smith).
Thus, potentially two study populations consisting of PS 2 or PS 3 NSCLC patients, not eligible for targeted agents (i.e. afatinib, erlotinib, gefitinib, crizotinib) due to underlying molecular alteratations, whose PS is impaired by their malignant disease may benefit from a novel concept of “patient-derived clinical benefit - guided chemotherapy for NSCLC”.
We propose to explore, whether up titration of weekly paclitaxel +/- carboplatin according to patients self-reported clinical benefit and toxicities is feasible and improves patient’s symptoms in the two different populations of PS 2 and PS 3 patients with untreated metastatic NSCLC. Small studies/series have shown, that weekly doses of paclitaxel 60-80 mg/m2 was well tolerated and active in patients with a PS 3 or worse and that paclitaxel doses of 50 mg/m2 are active. Therefore, these doses represent the starting doses. The target doses in the current proposal are derived from carboplatin/paclitaxel regimens previously published in clinical trials with patients in reduced PS.

Methods: Patients with untreated stage IV NSCLC with a PS of 2 or 3 and at least one symptom > 3 based on the Lung Cancer Symptoms Assessment scale (LCS) after one week of standardized supportive care treatment will be treated. In total, the enrolment of 10 patients (5 with a PS of 2 and 3 each) is planned at the cantonal hospital in St. Gallen. Functional Assessment of Cancer Therapy-Lung (FACT-L) and Trial Outcome Index (TOI; the sum of the physical, functional well-being, and LCS domains which are all part of the FACT-L) will be assessed every 4 weeks and 8 week, respectively. LCS will be performed every week to monitor patient-perceived clinical benefit. If patient related symptoms are stabilised or improved, higher grade toxicity (measured by CTCAE-PRO) is absent and the patient and treating physician (and nurses) believe in a sufficient success, doses of paclitaxel +/- carboplatin can be escalated weekly until the target dose level or clinical progression (i.e. worsening of the LCS by 3 or more points or the TOI by 6 or more points lasting for at least 4 consecutive weeks).

Aim: We hypothesize that the up titration of weekly paclitaxel +/- carboplatin according to the patients self-reported clinical benefit and toxicities is feasible and improves patient’s symptoms. A meaningful clinical benefit is defined by an improvement in the TOI by 6 or more points at 8 weeks compared to baseline.