Cancer-Related Fatigue, Version 2.2015 Berger, Ann M; Mooney, Kathi; Alvarez-Perez, Amy ...
Journal of the National Comprehensive Cancer Network
13, Številka:
8
Journal Article
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Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not ...proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer.
Background
Salvage immunochemotherapy followed by high‐dose chemotherapy and autologous stem cell transplantation is the standard‐of‐care second‐line treatment for patients with relapsed/refractory ...diffuse large B‐cell lymphoma after first‐line R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second‐line immunochemotherapy in patients with aggressive B‐cell lymphomas who relapse or are refractory to intensive first‐line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab R‐EPOCH, rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine R‐HyperCVAD, rituximab, cyclophosphamide, vincristine, doxorubicin, and high‐dose methotrexate alternating with ifosfamide, etoposide, and cytarabine R‐CODOX‐M/IVAC) remain unknown.
Methods
Outcomes of patients with non‐Burkitt, aggressive B‐cell lymphomas and relapsed/refractory disease after first‐line treatment with intensive immunochemotherapy regimens who received platinum‐based second‐line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression‐free survival (PFS) and overall survival (OS) from the time of receipt of second‐line immunochemotherapy.
Results
In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second‐line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first‐line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second‐line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second‐line immunochemotherapy.
Conclusions
Patients with early treatment failure after intensive first‐line immunochemotherapy experience poor outcomes after receiving standard second‐line immunochemotherapy. The use of standard‐of‐care or experimental therapies currently available in the third‐line setting and beyond should be investigated in the second‐line setting for these patients.
Patients with aggressive non‐Hodgkin lymphoma who fail intensive first‐line immunochemotherapy within 12 months experience poor outcomes with standard salvage immunochemotherapy. Standard‐of‐care and experimental therapies currently offered in the third‐line setting or later should be investigated earlier in this patient group.
Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is ...characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1–196), the 3‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3‐year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper‐CVAD or auto‐SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.
Idelalisib, an oral inhibitor of phosphatidylinositol-3-kinase δ (PI3Kδ), was evaluated in a 48-week phase 1 study (50-350 mg daily or twice daily) enrolling 40 patients with relapsed or refractory ...mantle cell lymphoma (MCL). Primary outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Patients without DLT and no evidence of disease progression after 48 weeks enrolled in the extension study. Patients had median age of 69 years (range, 52-83) and received median of 4 prior therapies (1-14); 17 of 40 patients (43%) were refractory to their most recent treatment. Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Common grade ≥3 adverse events (AEs) included (total%/grade ≥3%) diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite (20/15), upper respiratory infection (20/0), pneumonia (13/10), and alanine transaminase or aspartate transaminase elevations (60/20). ORR was 16 of 40 patients (40%), with CR in 2 of 40 patients (5%). Median DOR was 2.7 months, median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of concept that targeting PI3Kδ is a viable strategy and worthy of additional study in MCL. This trial was registered at www.clinicaltrials.gov as #NCT00710528.
•This clinical study assessed idelalisib, a selective PI3Kδ inhibitor, in 40 patients with relapsed/refractory MCL.•In a dose-escalation trial in heavily pretreated patients, an overall response rate of 40% was observed with an acceptable safety profile.
To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors.
An Expert Panel ...conducted targeted systematic literature reviews to identify new studies.
The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update.
The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.
Summary
While patients with double‐hit lymphoma (DHL) are now frequently treated with intensive front‐line immunochemotherapy, outcomes for those who fail these regimens and subsequently receive ...curative‐intent second‐line immunochemotherapy are unknown. We identified 55 such patients who achieved an overall/complete response rate of 29%/11%, median progression‐free/overall survival (PFS/OS) of 2/5·1 months and one‐year PFS/OS of 10/19% following the start of second‐line therapy. These outcomes may serve as a standard against which future second‐line treatment strategies for relapsed/refractory DHL can be measured and justify investigation of non‐cytotoxic therapies in the second‐line setting for these patients.
Summary
Patients with relapsed/refractory (R/R) non‐Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies ...suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment. Seventeen North American centres retrospectively queried records. The primary aim was to evaluate the overall response rate (ORR) to post‐CBT treatment. Secondary aims included progression‐free survival (PFS), duration of response (DOR) and overall survival (OS). Fifty‐nine patients (68% aggressive NHL, 69% advanced disease) were included. Patients received a median of three therapies before CBT. Fifty‐three (90%) discontinued CBT due to progression. Post‐CBT regimens included chemotherapy (49%), targeted therapy (30%), clinical trial (17%), transplant conditioning (2%) and chimeric antigen receptor T cell (CAR‐T) therapy (2%). The ORR to post‐CBT treatment was 51%, with median PFS of 6·1 months. In patients with at least stable disease (SD) to post‐CBT, the median DOR was significantly longer than to pre‐CBT (310 vs. 79 days, P = 0·005) suggesting sensitisation. Nineteen patients were transplanted after post‐CBT therapy. Median overall survival was not reached, nor affected by regimen. Prospective trials are warranted, as this may offer R/R NHL patients a novel therapeutic approach.
Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter ...phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.
Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-δ, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a ...median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (≥1 lymph nodes ≥5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414.
•This clinical study assessed idelalisib, a selective PI3Kδ inhibitor, in 64 patients with relapsed, indolent non-Hodgkin lymphoma.•Idelalisib treatment rapidly induced durable disease responses in heavily pretreated patients with a favorable safety profile.
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