Journey from oncologist to cancer survivor and patient advocate in the era of precision medicine.

In 2013, the American Association for Cancer Research (AACR) introduced the "Precision Medicine Series" of symposia. The goal of these conferences is to "highlight the incredible technology and advances in cancer research that together are enabling treatments that are precisely targeted to the unique molecular and genetic characteristics of an individual's cancer." This new series of AACR conferences reflects how patient treatment has evolved and continues to progress toward personalized treatments/medicine. It was in May of 2013 that I was diagnosed with a rare form of bladder cancer, plasmacytoid variant, for which survival statistics were grim, and the only genomic information available was the frequent somatic CDH1 loss-of-function mutation consistent with aggressive clinical behavior. The CDH1 gene encodes for E-cadherin, which plays a role in cell-cell adhesions and acts as a tumor suppressor when expressed normally. This information was subsequently published, but not until April 2016 (Al-Ahmadie et al. 2017. Nat Genet48: 356-358). At the time, I was a practicing medical oncologist and, ironically, urologic cancers had been my area of interest, dating back to my fellowship at Memorial Sloan Kettering Cancer Center (MSKCC) in 1981. I decided to return to MSKCC for treatment based on their experience with rare urologic cancers as well as my own personal connection.

Achieving Coordinated Care for Patients With Complex Cases of Cancer: A Multiteam System Approach.

Patients with cancer with multiple chronic conditions pose a unique challenge to how primary care and specialty care teams provide well-coordinated, patient-centered care. Effectiveness of these care teams in providing optimal health care depends on the extent to which they coordinate their goals and knowledge as components of a multiteam system (MTS). This article outlines challenges of care coordination in the context of an MTS, illustrated through the care experience of "Mr Fuentes," a patient in the Dallas County integrated safety-net system, Parkland. As a continuing patient with chronic illnesses, the patient being discussed is managed through one of the Parkland community-oriented primary care clinics. However, a cancer diagnosis triggered an additional need for augmented coordination between his different provider teams. Further research and practice should investigate the relationships of MTS coordination for shared care management, transfer to and from specialty care, treatment compliance, barriers to care, and health outcomes of chronic comorbid conditions, as well as cancer control and surveillance.

Oral versus intravenous administration of vinorelbine as a single agent for the first-line treatment of metastatic nonsmall cell lung carcinoma (NSCLC): A randomized phase II trial.

OBJECTIVES: Many patients with metastatic nonsmall cell lung carcinoma (NSCLC) cannot tolerate intravenous chemotherapy. Orally active agents would be more convenient and thus could improve their quality of life. METHODS: A total of 189 patients were randomized 2:1, 181 patients received treatment, 120 PO and 61 IV vinorelbine, 158 patients had stage IV and 31 stage IIIB disease. Among patients who received PO vinorelbine, the median age was 72 years, 62% were males; the Karnofski Performance Status (KPS) was 80-100 in 71%. These compare with a median age of 70 years, 56% male, and KPS of 80-100 in 65% of patients who received IV vinorelbine. Oral vinorelbine 60 mg/m2 was to be dose-escalated to 70 mg/m2 after the initial 3-weekly doses if there was no unacceptable toxicity. Intravenous vinorelbine was to be given 30 mg/m2 weekly. RESULTS: Five patients (4%) on PO and 8 (13%) on IV vinorelbine had a confirmed partial response, 56 (44%) and 29 (46%) had stable disease, respectively. Median time-to-disease-progression was 16.6 weeks (PO) versus 23.9 weeks (IV), and the median survival was 26 weeks (PO) versus 40.9 weeks IV vinorelbine. Median survival on PO vinorelbine for patients with KPS 60-70 was 8.3 weeks versus 43 weeks (IV). On PO vinorelbine 59 patients (57%) were dose escalated, 9 (7.5%) were dose reduced, and 10 (8.3%) did not receive PO vinorelbine at week 4. Pharmacokinetic studies confirmed PO vinorelbine exposure was significantly less than IV exposure. CONCLUSION: The inability to escalate the dose of PO vinorelbine above 60 mg/m2 weekly resulted in inferiority to IV vinorelbine at 30 mg/m2 weekly, especially in patients with poor performance status.

Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07.

PURPOSE: The randomized, multicenter, phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin (FULV) versus FULV with oxaliplatin (FLOX) in stage II or III colon cancer. Definitive analysis revealed an increase in 4-year disease-free survival from 67.0% to 73.2% in favor of FLOX. This study compares neurotoxicity between the treatments. PATIENTS AND METHODS: Neurotoxicity was recorded for all patients using standard adverse event reporting. Patients at select institutions completed a neurotoxicity questionnaire through 18 months of follow-up. RESULTS: A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported substudy. Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study (P < .0001). During therapy, patients receiving oxaliplatin experienced significantly more hand/foot toxicity (eg, "quite a bit" of cold-induced hand/foot pain 26% FLOX v 2.6% FULV) and overall weakness (eg, moderate weakness in 27.4% FLOX v 16.2% FULV). At 18 months, hand neuropathy had diminished, but patients who received oxaliplatin experienced continued foot discomfort (eg, moderate foot numbness and tingling for 22.1% FLOX v 4.6% FULV). Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor. Sixty-eight percent in the FLOX group v 8% in the FULV group had neurotoxicity at their first on-treatment assessment. Time to resolution was significantly longer for those receiving oxaliplatin, and continued beyond 2 years for more than 10% in the oxaliplatin group. CONCLUSION: Oxaliplatin causes significant neurotoxicity. It is experienced primarily in the hands during therapy and in the feet during follow-up. In a minority of patients the neurotoxicity is long lasting.