Patients with advanced, incurable cancer receiving anticancer treatment often experience multidimensional symptoms. We hypothesize that real-time monitoring of both symptoms and clinical syndromes ...will improve symptom management by oncologists and patient outcomes.
In this prospective multicenter cluster-randomized phase-III trial, patients with incurable, symptomatic, solid tumors, who received new outpatient chemotherapy with palliative intention, were eligible. Immediately before the weekly oncologists' visit, patients completed the palm-based E-MOSAIC assessment (Edmonton-Symptom-Assessment-Scale, ≤3 additional symptoms, estimated nutritional intake, body weight change, Karnofsky Performance Status, medications for pain, fatigue, nutrition). A cumulative, longitudinal monitoring sheet (LoMoS) was printed immediately. Eligible experienced oncologists were defined as one cluster each and randomized to receive the immediate print-out LoMoS (intervention) or not (control). Primary analysis limited to patients having uninterrupted (>4/6 visits with same oncologist) patient–oncologist sequences was a mixed model for the difference in patients global quality of life (G-QoL; items 29/30 of EORTC-QlQ-c30) between baseline (BL) and week 6. Intention-to-treat (ITT) analysis included all eligible patients.
In 8 centers, 82 oncologists treated 264 patients (median 66 years; overall survival intervention 6.3, control 5.4 months) with various tumors. The between-arm difference in G-QoL of 102 uninterrupted patients (intervention: 55; control: 47) was 6.8 (P = 0.11) in favor of the intervention; in a sensitivity analysis (oncologists treating ≥2 patients; 50, 39), it was 9.0 (P = 0.07). ITT analysis revealed improvement in symptoms (difference last study visit–BL: intervention -5.4 versus control 2.1, P = 0.003) and favored the intervention for communication and coping. More patients with high symptom load received immediate symptom management (chart review, nurse–patient interview) by oncologists getting the LoMoS.
Monitoring of patient symptoms, clinical syndromes and their management clearly reduced patients' symptoms, but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution.
Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with ...newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns.
Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern.
Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039).
Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.
•Many young women desire future biologic children after breast cancer.•Sixty-four percent of study patients had fertility concerns.•A low proportion of patients took fertility preservation measures.•Women treated with chemotherapy reported greater physical and sexual difficulties.•Women with stable relationships reported less psychosocial problems than single women.
Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of ...mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S.
Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments.
A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% 95% confidence interval (CI) 54–83 and 68% (95% CI 53–81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E.
No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted.
NCT01005199.
To determine whether the combination of nab-paclitaxel with gemcitabine has activity in patients with pretreated soft tissue sarcoma (STS).
NAPAGE is a phase Ib/II clinical trial investigating the ...combination of nab-paclitaxel (nab-pc) with gemcitabine employing two cohorts. One of a dose-de-escalation phase and one of expansion. In phase I, nab-pc was given at 150 mg/m
in combination with gemcitabine 1000 mg/m
every two weeks, until disease progression or unacceptable toxicity. This dose was recommended for phase II (RP2D), as there was no dose limiting toxicity (DLT) or discontinuations due to adverse events (AEs). The primary endpoint of the phase II was progression-free rate (PFR) at 3 months (H0: 20%, H1:40%). The secondary endpoints included progression free survival (PFS), overall survival (OS), AEs, objective response and patient-reported outcomes (PRO). Efficacy analysis was by intention to treat.
The 3-month PFR was 56.4% (95% confidence interval CI: 39.6-72.2%). The 3-month and 6-month PFS were 58.4% (95% CI: 41.3-72.1%) and 44.6% (95% CI: 28.4-59.5%), respectively. Median PFS was 5.3 months (95% CI: 1.4-8.2) and median OS was 12.8 months (95% CI: 10.5-39.2). The most common treatment-related grade ≥ 3 AE were neutropenia (18%), followed by anemia (2.6%), hypertension (2.6%) and alanine aminotransferase increase (2.6%). Grade 1 and grade 2 peripheral sensory neuropathy (PNP) occurred in 15.4% and 20.5%, respectively. No grade 3-4 PNP was reported.
Combining nab-pc and gemcitabine is safe. Promising activity is observed in pretreated STS patients with manageable toxicity. This regimen should be considered for further exploration.
Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in ...extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment.
SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5).
Intention-to-treat population included 4851 women in SOLE (n = 2425 in the intermittent and n = 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n = 78 in the intermittent and n = 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.
Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
•Disease-free survival after 7 years was similar with extended intermittent or continuous letrozole in breast cancer.•Circulating estrogen level was restored 6 weeks after interruption of extended letrozole treatment.•Extended intermittent letrozole treatment is safe for postmenopausal women with hormone receptor-positive breast cancers.•Results coupled with reported quality-of-life data should be reassuring for patients who need to interrupt extended therapy.
Weighing risks and benefits is currently the primary criterion for decisions regarding systemic anticancer treatment (SACT) in far advanced cancer patients, also in the modern immunotherapy- and ...molecular-targeted driven oncology. Decision aids rarely include substantially key concepts of early integrated palliative care (PC) and communication science. We compiled decisional factors (DFs) important for guiding the use of SACT with palliative intent (SACT-PI) and explored these DFs regarding their applicability in routine clinical care.
Clinician (participants: n = 28) and patient (n = 15) focus groups were conducted in an integrated oncology and PC setting. Thematic analysis was used to identify DFs. A Delphi survey of clinicians ranked the importance of DFs in routine decision-making. DFs were aligned with elements of the typical decision-making process, resulting in an eight-step guide for making SACT-PI decisions in clinical practice.
Eight focus groups revealed 55 DFs relating to established topics like providing information and risk–benefit analysis, as well as to PC topics like patients’ attitudes, beliefs, and hopes; patient–physician interaction; and physician attitudes. Agreement on the relative importance was reached for 34 (62%) of 55 DFs, assigned to five elements: patient/family, clinicians/system, patient-clinician-interaction, information/patient education, risk–benefit weighting/actual decision. These themes are embedded in a potential clinically useful SACT-PI Decision Framework, which includes eight steps: assess, educate, verify, reflect, discuss, weigh, pause, and decide.
The SACT-PI Decision Framework integrates subjective patient factors, interpersonal factors, and PC issues into decision-making. Our findings complement existing decision aids and prompt lists by framing DFs in the context of SACT-PI and enforce the decision ‘process’, not the decision act. Further research is needed to explore the relative importance of DFs in specific patient situations and test structured decision-making processes, such as our SACT-PI Decision Framework, against standard care.
•Patient-centered decisions in advanced cancer care demand a stepwise decisional process, not a single decision act.•The decision process includes key palliative care domains, e.g. illness understanding, symptom control, or end-of-life preparation.•Patients’ attitudes, beliefs, hopes, patient–physician interaction, and physician attitudes demand structured observation.•The SACT-PI Decision Framework includes concrete steps: assess, educate, verify, reflect, discuss, weigh, pause, decide.•Interprofessionally working oncology clinicians may transform decision-making processes in oncology beyond decision aids.
The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short ...induction at conventional doses.
Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%.
In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9months 90% confidence interval CI 6.8–8.4 in arm A, 9.0months (90% CI 8.1–10.9) in arm B and 8.5months (90% CI 6.7–9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms.
The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC.
Registration: ClinicalTrials.gov NCT01746225
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