Purpose The survival of patients with liver metastases from solid tumors is poor. We conducted a phase I study of hepatic arterial infusion (HAI) paclitaxel in patients with advanced cancer and predominant liver involvement. Methods Patients were treated with HAI paclitaxel 150–275 mg/m2 (and 15,000 IU heparin intraarterially) every 28 days. A “3 + 3” study design was used. Results Twenty-six patients were treated (median age, 59 years). Diagnoses were colorectal cancer (n = 10), breast cancer (n = 7), and other (n = 9). The median number of prior therapies was four (range, 0–10). The maximum tolerated dose (MTD) was HAI paclitaxel 225 mg/m2. Dose-limiting toxicities (DLTs) included Grade 3 neuropathy (1 of 5 patients) at HAI paclitaxel 275 mg/m2 and Grade 4 thrombocytopenia and neutropenia, and Grade 3 mucositis (1 of 4 patients) at 250 mg/m2. None of the eight patients treated with HAI paclitaxel 225 mg/m2 experienced a DLT. The most common toxicities were nausea and peripheral neuropathy. Of 22 patients evaluable for response, 3 (13.6%) patients had SD for ≥4 months (colorectal cancer, n = 1; thyroid cancer, n = 1; and hepatocellular carcinoma, n = 1; duration of response was 4 months, 7.1 months, and 22.2+ months, respectively). Conclusion The MTD of HAI paclitaxel was 225 mg/m2. This regimen was well tolerated and had antitumor activity in selected patients.

Purpose Patients with brain metastases are often excluded from clinical trials, but it is unclear if they pose an enhanced risk. Experimental Design We reviewed the records of 1,181 consecutive patients, with and without brain metastases, treated in our Phase I Clinical Trials Program. Results Ninety-three patients had brain metastases at the time of referral. Their median age was 54 years; median follow-up, 8 months. The rates of stable disease ≥ 4 months, partial, and complete response combined in patients with and without brain metastases were 17% and 27%, respectively (p= 0.03). Although the median survival of patients with brain metastases was shorter than that of patients without brain metastases (7.5 vs. 10.3 months; p = 0.002), in multivariate analysis the presence of brain metastases was not an independent factor predicting survival. There was no difference in time-to-treatment failure (1.74 vs. 1.84 months, respectively; p = 0.61) or in Grade 3-4 toxicity rates (including neurologic) (12% vs. 10%, respectively; p = 0.77) between patients with and without brain metastases. Conclusions The rates of survival and response of patients with brain metastases were lower than those for other patients in the phase I setting, but the presence of brain metastases was not an independent prognostic factor predicting survival, indicating that other covariates that co-exist with brain metastases were more significant. Time-to-treatment failure for patients with brain metastases was not decreased, nor was the incidence of serious adverse effects (including neurologic toxicity) increased, suggesting that these patients should be eligible for early clinical trials.

Regular physical activity reduces the burden of chronic diseases in older adults, but the majority of this population is relatively sedentary. Individuals considering a change in behavior, such as increasing exercise, often experience a mental state of ambivalence, which can lead to inaction. Ambivalence is resistant to traditional counseling methods used in medical settings, such as patient education. Motivational interviewing (MI) is a conversational style that has been shown to help overcome ambivalence by guiding patients to voice their personal reasons for change. Nurse practitioners are uniquely positioned to use MI with older adults to address ambivalence toward increasing physical activity.

CCR Translation for This Article from Phase I Clinical Trial Outcomes in 93 Patients with Brain Metastases: The MD Anderson Cancer Center Experience

CCR Translation for This Article from Phase I Clinical Trial Outcomes in 93 Patients with Brain Metastases: The MD Anderson Cancer Center Experience