Relationships of emerging biomarkers of cancer cachexia with quality of life, appetite, and cachexia.

PURPOSE: Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin 8 (IL-8), C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Baseline differences and significant relationships were explored for biomarkers with QoL, appetite, and cachexia. METHODS: In a prospective case-control, age and sex matched study, the European Organisation for the Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC-QLQ-C30) for QoL, the Functional Assessment of Anorexia and Cachexia Therapy assessment (FAACT A/CS-12) for appetite, and a five-factor cachexia assessment tool for cachexia assessment were performed. Routine hematological measurements and blood chemistry analyses together with ELISA procedures and a Multiplex® bead array platform, were used for biomarker analysis. Descriptive statistics and regression analyses were undertaken. P < 0.05 defined statistical significance. RESULTS: Global health status (QL-G), functional scales (QL-FS), and symptom scales (QL-SS) differed for cases and controls (p < 0.01). In cases, differences were observed for QL-G (p < 0.01), QL-FS (p < 0.01), and QL-SS (p = 0.01) compared to standardized references values. FAACT A/CS-12 scores differed significantly between cases and controls (p < 0.01) and 30% of cases scored "poor" appetites. Cachexia was present in 60% of cases. Albumin, lymphocytes, platelets, Hb, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), CRP, TNFα, all at p < 0.01, neutrophil to lymphocyte ratio (NLR) (p = 0.02), IL-6 (p < 0.04), and IL-8 (p = 0.02) differed significantly between cases and controls. No difference was found for CXCL5 or H3Cit. Albumin NLR, Hb, PLR, SII, TNFα, IL-8, and CRP showed significant relationships with all aspects of QoL. QL-FS was significantly related to CXCL5 (p = 0.04), significant relationships with FAACT A/CS-12 included: NLR (p = 0.002), Hb (p < 0.001), and PLR (p < 0.01). NLR, PLR, SII, TNFα, IL-6, IL-8, and CRP correlated positively to cachexia and albumin while Hb and lymphocyte count correlated negatively to cachexia. CONCLUSION: CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia, nor significantly related to QoL, appetite or cachexia. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8, and CRP were reliable indicators of QoL, appetite, and cachexia. Future research should include other novel biomarkers namely growth differentiation factor-15 (GDF-15), fibroblast growth factor 21 (FGF-21), fractakline, interferon gamma (IFN-y), IL-16, macrophage colony stimulating factor (M-CSF), and macrophage procoagulant-inducing factor (MPIF).

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial.

BACKGROUND: To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC. PATIENTS AND METHODS: In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25-120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0-120 and 0-24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points. RESULTS: The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated. CONCLUSION: Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population. CLINICALTRIALSGOV: NCT01594749 (https://clinicaltrials.gov/ct2/show/NCT01594749).

Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia: a pilot study.

The soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is a useful marker of infection in patients with sepsis, but has not been adequately evaluated in patients with chemotherapy-associated febrile neutropenia (FN). The value of sTREM-1 in this setting has been tested in a retrospective, pilot study using stored serum from 48 cancer patients with documented FN. On presentation, patients were categorized according to the Talcott risk-index clinical score. Circulating soluble sTREM-1 was measured using an ELISA procedure, while procalcitonin (PCT) or interleukins 6 (IL-6) and 8 (IL-8), included for comparison, were measured using an immunoluminescence-based assay and Bio-Plex® suspension bead array system, respectively. Circulating concentrations of both sTREM-1 and PCT were significantly (P < 0.05) elevated in patients at high risk for complications or death, as predicted by the Talcott score and were significantly lower in patients who responded to empiric antimicrobial agents. Neither IL-6 nor IL-8 accurately predicted serious complications in patients with FN. These observations, albeit from a pilot study, demonstrate that sTREM-1 is indeed elevated in high-risk patients with FN and is potentially useful to predict their clinical course, either together with, or as an alternative to PCT.

Supportive care in patients with cancer during the COVID-19 pandemic.

Cancer care has been profoundly impacted by the global pandemic of severe acute respiratory syndrome coronavirus 2 disease (coronavirus disease 2019, COVID-19), resulting in unprecedented challenges. Supportive care is an essential component of cancer treatment, seeking to prevent and manage chemotherapy complications such as febrile neutropenia, anaemia, thrombocytopenia/bleeding, thromboembolic events and nausea/vomiting, all of which are common causes of hospitalisation. These adverse events are an essential consideration under routine patient management, but particularly so during a pandemic, a setting in which clinicians aim to minimise patients' risk of infection and need for hospital visits. Professional medical oncology societies have been providing updated guidelines to support health care professionals with the management, treatment and supportive care needs of their patients with cancer under the threat of COVID-19. This paper aims to review the recommendations made by the most prominent medical oncology societies for devising and modifying supportive care strategies during the pandemic.

Phase II study of pegylated liposomal doxorubicin and carboplatin in patients with platinum-sensitive and partially platinum-sensitive metastatic ovarian cancer.

OBJECTIVE: This phase II study assessed the activity and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin in relapsed ovarian cancer (ROC). METHOD: Forty women with platinum-sensitive and partially platinum-sensitive ROC were treated with PLD 50 mg/m2 plus carboplatin area under the curve 5 every 28 days in this South African multicenter study. All patients who completed 3 cycles of chemotherapy were evaluated for response. Primary outcome was response in the intent-to-treat population. RESULTS: Complete response was 35%, and partial response was 32.5% (overall response, 67.5%). Median time-to-progression was 11.9 months, and median survival was 30.0 months. Overall response was higher in platinum-sensitive (81%) versus partially platinum-sensitive patients (53%), as were median duration of response, median time-to-progression, and median survival. Treatment was well tolerated, with no grade 4 nonhematologic toxicities. Grade 3/4 hematologic toxicities included leukopenia (58%), neutropenia (55%), and thrombocytopenia (43%). CONCLUSION: Pegylated liposomal doxorubicin plus carboplatin is well tolerated and active in the treatment of platinum-sensitive and partially platinum-sensitive ROC.

Trisomy 5 in Ph+ chronic myeloid leukemia in association with megakaryocytosis.

A patient with a megakaryocytosis associated with a Philadelphia chromosome-positive chronic myeloid leukemia (CML) was found to have a trisomy of chromosome five. To our knowledge, this is the first case of trisomy 5 associated with a Ph + CML, particularly one with a megakaryocytosis. The trisomy 5 may be associated with the resistance to cytostatic drugs found in this patient.

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study.

The aim of this multicentric phase II study was to investigate the efficacy and toxicity of a combination of chemotherapy containing paclitaxel (Taxol) and a novel compound, a liposomal encapsulated doxorubicin (Caelyx), as first line therapy for patients with metastatic breast cancer. Thirty-four patients with advanced breast cancer were treated with a combination of paclitaxel 175 mg/m2 and liposomal doxorubicin 30 mg/m2, every 3 weeks. The combination chemotherapy was effective in 73% of the patients (ITT) (95% CI 55-86%) (7 complete and 18 partial responses). Grade 3/4 toxicities were documented in a small number of patients. Two toxic deaths (6%) were documented, one a hepatorenal failure and another a febrile neutropenia. One patient experienced pulmonary embolism but continued on treatment after appropriate therapy. The combination of paclitaxel and liposomal encapsulated doxorubicin induces a high and durable response rate with a moderate toxicity profile.

A phase II study of idarubicin and prednisone in multiple myeloma.

Twenty-one patients with multiple myeloma were treated with idarubicin 45 mg/m2 orally day 1 and prednisone 60 mg/m2 day 1-4 every three weeks. Moderate to severe gastrointestinal and hematopoietic toxicity were observed. Twelve of the twenty-one patients had relapsed on prior treatment. Of these, 2 patients responded. Two patients had primary resistant disease, neither responded. Seven patients had received no prior treatment, three responded. Idarubicin and prednisone have modest activity in refractory myeloma, with short duration of response and severe toxicity.

Prediction of outcome in cancer patients with febrile neutropenia: comparison of the Multinational Association of Supportive Care in Cancer risk-index score with procalcitonin, C-reactive protein, serum amyloid A, and interleukins-1beta, -6, -8 and -10.

The primary objective of the study was to compare the predictive potential of procalcitonin (PCT), C-reactive protein (CRP), serum amyloid A (SAA), and interleukin (IL)-1beta, IL-6, IL-8, and IL-10, with that of the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score in cancer patients on presentation with chemotherapy-induced febrile neutropenia (FN). Seventy-eight consecutive FN episodes in 63 patients were included, and MASCC scores, as well as concentrations of CRP, SAA, PCT, and IL-1beta, IL-6, IL-8 and IL-10, and haematological parameters were determined on presentation, 72 h later and at outcome. Multivariate analysis of data revealed the MASCC score, but none of the laboratory parameters, to be an accurate, independent variable (P < 0.0001) for prediction of resolution with or without complications and death. Of the various laboratory parameters, PCT had the strongest association with the MASCC score (r = -0.51; P < 0.0001). In cancer patients who present with FN, the MASCC risk-index score is a useful predictor of outcome, while measurement of PCT, CRP, SAA, or IL-1beta, IL-6, IL-8 and IL-10, is of limited value.

Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy.

BACKGROUND: Anthracycline-induced cardiotoxicity has led to the adoption of empirical dose limits that may restrict continued use of anthracyclines among patients who might benefit. Dexrazoxane, a cardioprotective agent, has been shown to reduce the risk of anthracycline-associated cardiotoxicity when given from first dose of anthracycline. This study sought to confirm the benefit of dexrazoxane in patients at high risk of cardiotoxicity due to prior anthracycline use. PATIENTS AND METHODS: A total of 164 female breast cancer patients, previously treated with anthracyclines, received anthracycline-based chemotherapy either with (n = 85) or without (n = 79) dexrazoxane for a maximum of six cycles. RESULTS: Compared with those receiving anthracycline alone, patients treated with dexrazoxane experienced significantly fewer cardiac events (39% versus 13%, P < 0.001) and a lower and less severe incidence of congestive heart failure (11% versus 1%, P < 0.05). Tumor response rate was unaffected by dexrazoxane therapy. The frequency of adverse events was similar between groups and there were no significant between-group differences in the number of dose modifications/interruptions. CONCLUSION: Dexrazoxane significantly reduced the occurrence and severity of anthracycline-induced cardiotoxicity in patients at increased risk of cardiac dysfunction due to previous anthracycline treatment without compromising the antitumor efficacy of the chemotherapeutic regimen.

Phase II clinical study of pirarubicin in hormone resistant prostate cancer.

Twenty one patients with hormone resistant prostate cancer were entered in a phase II study of pirarubicin 70 mg/m2, as a single intravenous injection given at 21 day intervals. All patients had leukopenia (9 severe or life threatening) and 2 died of septicemia. Thrombocytopenia occurred in 5 patients (one life threatening) and anemia in 12 patients. One partial response of 3 months duration was documented. Pirarubicin 70 mg/m2 given intravenously at 21 day intervals causes severe hematological toxicity and has minimal therapeutic activity in patients with hormone resistant prostate cancer.

Small cell lung cancer: analysis of factors influencing the response to treatment and survival.

The aims of this study were to identify prognostic factors in patients (pts) with small cell lung cancer and to identify dominant prognostic factors independent of disease stage, to define prognostic subsets through recursive partitioning and amalgamation (RPA) and to analyze the clinical characteristics of long-term survivors. The prognostic significance of 27 pre-treatment variables was evaluated in 144 pts seen at a single institution. The current study confirmed the superior outcome for pts with limited disease (LD) in terms of response, response duration, time to treatment failure and survival when compared to those with extensive disease (ED). None of the variables independently predicted for response in patients with LD. Response correlated significantly with a good performance status (PS) for pts with ED and for the whole group. A good PS was the most significant predictor for prolonged survival in pts with LD. In ED a longer survival was associated with a normal pre-treatment albumin value, absence of weight loss and female gender. When the whole group was considered, PS and number of metastatic sites were identified as the most influential factors for survival independent of disease stage. RPA analysis defined 3 prognostic subsets based on stage of disease, PS and number of metastatic sites. The best survival rates were seen in pts with LD with a good PS and pts with ED, only one metastatic site and a good PS. 11% of pts survived > 2 years (18% LD, 6% ED). A complete response to chemotherapy was the most important predictor for long-term survival. Comparison of the data from this study with published results of protocol studies showed similar outcomes.

Prognostic factors affecting the survival of patients with multiple myeloma. A retrospective analysis of 86 patients.

A retrospective analysis of data concerning 86 patients with multiple myeloma was carried out in order to evaluate factors affecting survival. The overall median survival was 621 days. In a univariate analysis the following factors were significantly associated with poor survival: serum creatinine greater than or equal to 150 mmol/l, haemoglobin less than 11 g/dl and serum calcium values greater than 2.75 mmol/l; and Eastern Cooperative Oncology Group performance status 3-4. However, age, sex, Durie and Salmon staging, lytic lesions, serum immunoglobulin concentration, urine Bence Jones protein, percentage of plasma cells in the bone marrow, proteinuria, and type of chemotherapy given were not significantly associated with survival. A strong prediction of survival was found by grouping the serum creatinine and haemoglobin levels of patients at presentation.

Repeated use of granisetron in patients receiving cytostatic agents.

BACKGROUND: Granisetron was shown to be a safe and effective antiemetic agent when given with initial cytostatic therapy. This study was undertaken to investigate the efficacy and safety of the continued use of granisetron. METHODS: Ninety-one patients were given 438 cycles of granisetron during subsequent courses of cytostatic treatment. In 56 patients, 40 micrograms/kg i.v. was given in 159 cycles, and in 42 patients, 3 mg i.v. was given in 279 cycles. In patients having breakthrough symptoms, as many as two rescue doses were given to re-establish control. RESULTS: Overall objective control of nausea and vomiting was observed in 88.6% of the 40 micrograms/kg-cycles and in 90.32% of the 3-mg cycles. In the 438 cycles given, complete control was achieved in 105 of 159 (66%) of the 40-micrograms/kg cycles and in 217 of 279 (77.78%) of the 3-mg cycles. Thirty-three patients received 97 cycles of cisplatin-based regimens. The objective control rate was 82.47% (80 of 97 cycles) in these patients. The control rate in patients receiving regimens not containing cisplatin was 94.4% (322 of 341 cycles). Rescue doses improved or resolved symptoms in 53 of 61 (86.9%) cycles. No statistically significant difference in nausea and vomiting control was seen between men and women or between the different age groups. The only toxicities encountered were headache in 14 of 438 (3.2%) cycles and mild constipation in 8 of 438 (1.8%) cycles. CONCLUSION: Granisetron is safe and well tolerated, maintains its antiemetic efficacy after repeated cycles of therapy, and is effective as an interventional treatment for nausea and vomiting.

Survival determinants in patients with advanced ovarian cancer.

An analysis was performed on 127 consecutive women with advanced measurable ovarian cancer to evaluate factors predicting for survival. All patients received cis-platinum-based chemotherapy as treatment for stage IIIB to stage IV disease. Eighteen clinical, radiological, and biochemical parameters were subjected to univariate and multivariate analyses. Recursive partitioning and amalgamation (RPA) was used to define prognostic subsets with different survival potentials. In the univariate analysis, factors that predicted for survival were weight loss, histology, stage, number of metastases, presence of ascites, size of the residual tumor, and rate of tumor response. When these significant variables were included in a Cox model, advanced stage of disease, histology other than adenoserous carcinoma, the presence of tumor bulk, and a slow rate of tumor response independently predicted a poorer survival. Using the three disease-related prognostic variables, a RPA model was derived and three groups were identified with median survival times of 76, 28, and 21 months, respectively (P = 0.001). The best survival time of 76 months was seen in patients with stage III, nonbulky, adenoserous ovarian carcinoma. It is concluded that the rate of tumor response is important in predicting the outcome of patients with ovarian cancer. Furthermore, the interactions between prognostic factors are emphasized by the RPA model and a subgroup of patients with a projected 10-year survival of 50% is identified.

Plasma melatonin in patients with breast cancer.

Daytime plasma melatonin values were measured by radioimmune assay in 86 patients with breast cancer; 280 assays were done and compared with the clinical status of the patients. Patients in the advanced disease group had significantly higher levels than those in the adjuvant treatment group, and patients with progressive disease had significantly higher values than those in remission or with stable disease. No significant differences were found between different dominant metastatic disease sites. Multiple-regression tests showed a significant inverse correlation between survival and melatonin values.