Repeated Chemotherapy Cycles Research Articles

Study on knowledge of chemotherapy's adverse effects and their self-care ability to manage - The cancer survivors impact

IntroductionCancer is the second leading cause of death globally. Adverse effects of chemotherapy affect physiological and psychological aspects of human life. Self-care practice to manage side effects can improve the quality of life. AimsThe study investigates the relationship between knowledge on the adverse effects of chemotherapy and self-care ability to manage chemotherapy survivors' side effects. Subjects and methodsThis was a single centre, Cross-sectional, descriptive study. A face-to-face interview guided by a structured questionnaire was conducted among 100 cancer patients admitted at the daycare centre to receive repeated chemotherapy cycles. Information gathered included knowledge on chemotherapy and its adverse effects and self-care ability to manage them. ResultsResults indicated 58% had an above-average level of experience on chemotherapy and side effects,16.42 ± 3.56 Vs 8.52 ± 3.37.To overcome hair loss, 77% of patients preferred to use a wig/scarf to cover the head. To reduce nausea and vomiting symptoms, 48% chose to consume less food. Knowledge on side effects of chemotherapy moderate positively related to self-care practices with (r = 0.55,p = 0.001 level), which shows a significant raise on knowledge level will improve their self-care practices. Knowledge of the adverse effects of chemotherapy was not associated with the demographic variables of study participants. ConclusionStudy concluded that it was essential to enhance awareness and overcome adverse chemotherapy effects via counselling services using current modalities for better self-care practices.

How to win the ovarian cancer stem cell battle: destroying the roots.

Ovarian cancer has the highest mortality rate among gynecologic malignancies. The combination of cytoreductive surgery and chemotherapy is the standard regimen for the treatment of ovarian cancer. The initial treatment is usually effective, but many patients with ovarian cancer experience recurrence, and treatment options for recurrent disease remain challenging. Cancer stem cells (CSCs) are suggested to play an essential role in cancer recurrence after initial chemotherapy. Furthermore, they are of great interest as CSCs may also be involved in chemotherapy susceptibility. Thus, understanding the characteristics and mechanisms by which CSCs display resistance to therapeutic agents is important to design effective cancer treatments. In this review, we describe and discuss current therapeutic regimens for ovarian cancer, as well as the various CSC markers, association between CSCs and disease progression, correlation of CSCs with poor prognosis, enrichment of CSCs in tumor tissues following repeated chemotherapy cycles, activation of major signaling pathways following chemotherapy, and potential inhibitors that suppress these signaling cascades. In addition, clinical trials evaluating novel targeted therapies to overcome chemotherapy resistance will be reviewed. The combination of traditional chemotherapy and CSC-targeted therapy could be an effective and promising anticancer treatment for ovarian cancer. Understanding the biological properties of CSCs and the mechanism of chemotherapy resistance are critical to design and develop new therapeutic strategies to overcome CSC-associated chemotherapy resistance.

Effect of feedback regulation on stem cell fractions in tissues and tumors: Understanding chemoresistance in cancer

While resistance mutations are often implicated in the failure of cancer therapy, lack of response also occurs without such mutants. In bladder cancer mouse xenografts, repeated chemotherapy cycles have resulted in cancer stem cell (CSC) enrichment, and consequent loss of therapy response due to the reduced susceptibility of CSCs to drugs. A particular feedback loop present in the xenografts has been shown to promote CSC enrichment in this system. Yet, many other regulatory loops might also be operational and might promote CSC enrichment. Their identification is central to improving therapy response. Here, we perform a comprehensive mathematical analysis to define what types of regulatory feedback loops can and cannot contribute to CSC enrichment, providing guidance to the experimental identification of feedback molecules. We derive a formula that reveals whether or not the cell population experiences CSC enrichment over time, based on the properties of the feedback. We find that negative feedback on the CSC division rate or positive feedback on differentiated cell death rate can lead to CSC enrichment. Further, the feedback mediators that achieve CSC enrichment can be secreted by either CSCs or by more differentiated cells. The extent of enrichment is determined by the CSC death rate, the CSC self-renewal probability, and by feedback strength. Defining these general characteristics of feedback loops can guide the experimental screening for and identification of feedback mediators that can promote CSC enrichment in bladder cancer and potentially other tumors. This can help understand and overcome the phenomenon of CSC-based therapy resistance.

Repeated chemotherapy cycles produced progressively worse and enduring impairments in the sleep–wake profile of hospitalized breast cancer patients

ABSTRACT Cross-sectional studies, conducted previously, reported disruption of the sleep–wake rhythms of cancer patients on chemotherapy. Although few studies highlighted the effect of hospitalization on sleep, no data were obtained on the effects of longitudinal repeated chronotherapy cycles on sleep pattern of cancer patients. In this study, using the two-factor repeated-measures design, we attempted to assess longitudinally the quality and pattern in sleep–wake behavior of breast cancer in- and outpatients, who received multiple cycles of chemotherapy. We randomly selected the patients from the Regional Cancer Center, Dr. B.R. Ambedkar Memorial Hospital, Raipur, India. We used wrist-worn actigraphs to record the sleep–wake pattern both objectively and subjectively. Additionally, we administered Pittsburgh Sleep Quality Index questionnaire to each patient. Results revealed statistically significant effects of chemotherapy with and without hospitalization mostly on all objective [total sleep time, sleep onset latency, wake after sleep onset, fragmentation index, and sleep efficiency (SE)] and subjective [duration of sleep, sleep disturbance, sleep latency, daytime dysfunction due to sleepiness, SE, and overall sleep quality] sleep–wake parameters of cancer patients. Cancer patients, who received repeated chemotherapy administration followed by hospitalization on each occasion, experienced severely impaired sleep–wake cycle as compared with those who went home after receiving chemotherapy.

Rolapitant for the prevention of delayed nausea and vomiting over initial and repeat courses of emetogenic chemotherapy

ABSTRACTIntroduction: Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. Although sustained antiemetic control across repeated chemotherapy cycles is important for cancer treatment continuation, few studies have investigated the efficacy of antiemetic prophylaxis over multiple chemotherapy cycles.Areas covered: Here we discuss the use of antiemetic hydroxytryptamine type 3 (5-HT3) receptor and neurokinin (NK)-1 receptor antagonists for prevention of CINV, limiting our review to clinical trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1 receptor antagonist rolapitant. 5-HT3 receptor antagonists may be effective in controlling CINV over repeated chemotherapy cycles, but evidence comes primarily from noncomparative studies. NK-1 receptor antagonists provide increased protection against CINV but differences in endpoint selection and methods of analysis preclude meaningful comparisons between agents. Rolapitant shows sustained control of emesis and nausea over multiple cycles of chemotherapy, and compared to other NK-1 receptor antagonists, has a longer half-life and reduced potential for cytochrome P450 3A4-mediated drug-drug interactions.Expert commentary: Trial design should be a key consideration in future studies of CINV therapies, including analytical methods utilized, choice of endpoints, and methods for accounting for nonresponders and patient attrition over multiple cycles of chemotherapy.

Repeated cycles of 5-fluorouracil chemotherapy impaired anti-tumor functions of cytotoxic T cells in a CT26 tumor-bearing mouse model.

BackgroundRecently, the immunostimulatory roles of chemotherapeutics have been increasingly revealed, although bone marrow suppression is still a common toxicity of chemotherapy. While the numbers and ratios of different immune subpopulations are analyzed after chemotherapy, changes to immune status after each cycle of treatment are less studied and remain unclear.ResultsTo determine the tumor-specific immune status and functions after different cycles of chemotherapy, we treated CT26 tumor-bearing mice with one to four cycles of 5-fluorouracil (5-FU). Overall survival was not improved when more than one cycle of 5-FU was administered. Here we present data concerning the immune statuses after one and three cycles of chemotherapy. We analyzed the amount of spleen cells from mice treated with one and three cycles of 5-FU as well as assayed their proliferation and cytotoxicity against the CT26 tumor cell line. We found that the absolute numbers of CD8 T-cells and NK cells were not influenced significantly after either one or three cycles of chemotherapy. However, after three cycles of 5-FU, proliferated CD8 T-cells were decreased, and CT26-specific cytotoxicity and IFN-γ secretion of spleen cells were impaired in vitro. After one cycle of 5-FU, there was a greater percentage of tumor infiltrating CD8 T-cells. In addition, more proliferated CD8 T-cells, enhanced tumor-specific cytotoxicity as well as IFN-γ secretion of spleen cells against CT26 in vitro were observed. Given the increased expression of immunosuppressive factors, such as PD-L1 and TGF-β, we assessed the effect of early introduction of immunotherapy in combination with chemotherapy. We found that mice treated with cytokine induced killer cells and PD-L1 monoclonal antibodies after one cycle of 5-FU had a better anti-tumor performance than those treated with chemotherapy or immunotherapy alone.ConclusionsThese data suggest that a single cycle of 5-FU treatment promoted an anti-tumor immune response, whereas repeated chemotherapy cycles impaired anti-tumor immune functions. Though the amount of immune cells could recover after chemotherapy suspension, their anti-tumor functions were damaged by multiple rounds of chemotherapy. These findings also point towards early implementation of immunotherapy to improve the anti-tumor effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0167-7) contains supplementary material, which is available to authorized users.

5-HT3 receptors as important mediators of nausea and vomiting due to chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24–120h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy–induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

P182 NEPA, a new combination antiemetic, exhibits sustained efficacy over repeated chemotherapy cycles

P182 NEPA, a new combination antiemetic, exhibits sustained efficacy over repeated chemotherapy cycles

Profile of netupitant/palonosetron (NEPA) fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV).

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo®) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy.

NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting (CINV) following repeated chemotherapy cycles: Results of a phase III trial.

e20716 Background: NEPA is a fixed-dose combination of netupitant (NETU), a highly selective NK1 receptor antagonist and palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3receptor antagonist. Recent clinical trials have been conducted to definitively establish the superiority of the combination, NEPA, over single agent PALO in the prevention of CINV following a single cycle of highly (HEC) and moderately (MEC) emetogenic CT. This study was designed to examine the tolerability and efficacy of NEPA over multiple cycles of HEC and MEC. Methods: Trial design: multinational, randomized, double-blind, parallel group, phase III study assessing the safety and efficacy of a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) administered only on day 1 of each cycle, and given with concomitant oral dexamethasone on day 1 (with MEC) and days 1-4 (when given with HEC) prior to repeated cycles of HEC or MEC. A standard arm 3-day oral aprepitant + PALO + dexamethasone was included as a control group with an unbalanced 3:1 (NEPA : aprepitant) randomization ratio. There was no limit to the number of chemotherapy cycles allowed. Safety was the primary objective of the study as assessed by adverse events; secondary variables included ECGs, left ventricular ejection fraction, cardiac troponin levels and laboratory tests. Efficacy was assessed as the proportion of patients with complete response (no emesis, no rescue medication). Results: 413 patients were randomized in this study with the last patient visit occurring on 13 September, 2012. The analyses will be completed by March 2013 and will be fully available by ASCO 2013. Conclusions: Few large randomized trials have documented safety and efficacy of antiemetic control with multiple cycles of chemotherapy, and especially with HEC. The in depth safety profile will provide new information for all study arms over multiple cycles. NEPA is designed to provide maximal convenience while providing high degrees of antiemetic control throughout the patient’s full course of chemotherapy. Clinical trial information: NCT01376297.

Management of Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a serotonin 5-HT3 receptor antagonist, dexamethasone and a neurokinin 1 (NK1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Aprepitant, the first and only agent clinically available in the NK1 receptor antagonist drug class has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone to control CINV. Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US-FDA approved antipsychotic, has emerged in recent trials as an effective preventative agent for CINV, as well as a very effective agent for the treatment of breakthrough emesis and nausea. Clinical trials using gabapentin, cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

A Review of the Prevention of Nausea and Vomiting Induced by Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors significantly influence CINV. The use of a combination of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a unique mechanism of action, appears to be the most effective agent in its class. Aprepitant, the only agent clinically available in the drug class of NK-1 receptor antagonists, has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US Food and Drug Administration-approved antipsychotic, has emerged in recent trials as effective for the prevention of chemotherapy-induced emesis and nausea and for the treatment of breakthrough emesis and nausea. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multi-day chemotherapy and bone marrow transplantation.

Efficacy and Safety of Palonosetron in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients with Non-Hodgkin's Lymphomas Undergoing Repeated Cycles of Moderately Emetogenic Chemotherapy

Abstract 5196 Background:Patients undergoing chemotherapy (CT) commonly receive repeated cycles of treatment. While chemotherapy-induced nausea and vomiting (CINV) can be a disruptive, unwanted side effect with negative consequences on patient quality of life, possible discontinuation of therapy, and associated increased health care resources, prevention of CINV in cycle 1 diminishes its potential in subsequent cycles. Therefore, optimizing antiemetic prophylaxis at initiation of CT is critical. Palonosetron (PALO), a potent 5-HT3 receptor antagonist (RA) with a distinctly different pharmacokinetic and receptor binding profile, has demonstrated improved CINV protection compared to older 5-HT3 RAs in multiple phase 3 and 4 single-CT-cycle clinical trials; however, few studies have evaluated PALO over multiple cycles of CT. Methods:This was a prospective, multicenter, single-arm study designed to assess the efficacy and safety of single IV doses of PALO 0.25 mg in preventing CINV in chemotherapy-naïve patients with Non-Hodgkin’s Lymphomas (NHL) scheduled to receive at least 2 repeated, consecutive cycles of moderately emetogenic chemotherapy (CHOP, R-CHOP or ProMACE-CytaBOM). Corticosteroids were part of the CT regimen but not administered as an antiemetic. The primary efficacy endpoint was complete response (CR: defined as no emesis and no use of rescue medication) during the overall phase (0–120 h) following CT during each cycle. Secondary endpoints included CR during the acute (0–24 h) and delayed (24–120 h) time periods, as well as evaluation of proportion of emesis-free patients and nausea severity (according to a 100 mm VAS) during all 3 time intervals. The safety profile and adverse events were also assessed. Results:A total of 88 patients with either B-cell (91%) or T-cell (9%) NHL received PALO for a total of 317 CT cycles (mean 3.6; median 4). The majority of patients were white (99%) males (60%) with a mean age of 59.7 yrs who received either CHOP (47%) or R-CHOP (52%). CR rates during the acute, delayed and overall phases were sustained across the 4 CT cycles (Table). High proportions of patients remained emesis-free and experienced less than significant nausea (0 to <25 mm VAS) during the 5 days post-CT throughout repeated CT cycles (Table). PALO was well tolerated over repeated cycles, with few adverse events considered possibly/probably/definitely related (TRAEs: treatment related adverse events) (8% of patients; none serious). The incidence of the typically frequent TRAEs of headache and constipation was low (1% and 2%) and there were no unexpected or relevant differences in TRAEs between cycles or in later cycles (6%, 3%, 0%, 4% cycles 1–4, respectively).Efficacy EndpointCycle 1 (n = 88)Cycle 2 (n = 82)Cycle 3 (n = 78)Cycle 4 (n = 69)Total Cycles (N = 317)CR(0–24 h)77%84%82%84%82%(24-120 h)83%94%92%94%91%(0–120 h) (primary endpoint)68%81%78%81%77%No Emesis(0–24 h)91%94%96%94%94%(2419–>120 h)>89%95%94%96%93%(0–120 h)86%92%92%93%91%None/No Significant Nausea(0-24 h)94%94%96%94%95%(24–120 h)85%95%96%93%92%(0–120 h)83%92%94%91%90% Conclusion:A single, fixed IV dose of palonosetron was shown to be safe and effective in preventing CINV over repeated chemotherapy cycles in patients with NHL. Disclosures:Voisin:Helsinn Healthcare: Employment. Ballinari:Helsinn Healthcare: Employment.

A phase III open-label study to assess safety and efficacy of palonosetron for preventing chemotherapy-induced nausea and vomiting (CINV) in repeated cycles of emetogenic chemotherapy

Prevention of chemotherapy-induced nausea and vomiting (CINV) is of great importance for the completion of multiple cycles of cancer chemotherapy. Palonosetron is a second-generation 5-HT(3) receptor antagonist with proven efficacy for both acute and delayed CINV. This study was designed to assess the safety and efficacy of 0.75 mg palonosetron in repeated cycles of highly emetogenic chemotherapy or anthracycline-cyclophosphamide combination (AC/EC). We gave 0.75 mg palonosetron to 538 patients 30 min prior to ≥ 50 mg/m(2) cisplatin or AC/EC on day 1. Prophylactic dexamethasone was administered on days 1-3. The primary endpoint was the incidence rate of adverse events (AEs). The secondary endpoint was complete response rate (CR, defined as no emesis and no rescue medication) throughout the study period. Treatment-related AEs were seen in 44% (237 of 538 patients). Serious AEs were seen in 4% (23 of 538 patients), all considered unrelated or unlikely to be related to palonosetron. Only one patient discontinued the study due to a treatment-related AE. No trend toward worsening of AEs was observed in subsequent cycles of chemotherapy. Complete response rates were maintained throughout repeated cycles. The extraordinary safety profile and maintenance of efficacy of 0.75 mg palonosetron combined with dexamethasone were demonstrated throughout repeated chemotherapy cycles.

Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients with Cancer

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient characteristics (e.g., female gender, younger age, low alcohol consumption and history of motion sickness) are the major risk factors for CINV. This article provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, which has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared with the first-generation 5-HT(3) receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy and had a similar safety profile. Owing to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. This review provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist. The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Palonosetron has a longer half-life and a higher binding affinity than the first-generation 5-HT(3) receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first-generation 5-HT(3) receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials which were different from the common reactions reported for the 5-HT(3) receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation.

Palonosetron: a second generation 5-hydroxytryptamine 3 receptor antagonist

Background: Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. Objective: This review provides a detailed description of palonosetron, a second generation 5-HT3 receptor antagonist. Methods: The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Results/conclusion: Palonosetron has a longer half-life and a higher binding affinity than the first generation 5-HT3 receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials that were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation.

Antiemetic control: toward a new standard of care for emetogenic chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone have significantly improved the control of acute CINV, but delayed CINV remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have been approved for the prevention of both acute and delayed CINV. Palonosetron is a second-generation 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 (NK-1) receptor antagonists. Casopitant is another NK-1 receptor antagonist that is under review by the FDA after recent completion of Phase III clinical trials. The introduction of these new agents has generated revised antiemetic guidelines for the prevention of CINV. Future studies may consider the use of palonosetron, aprepitant and casopitant with other antiemetic agents (olanzapine, gabapentin, cannabinoids) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Pharmacological Management of Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors significantly influence CINV. Serotonin 5-HT(3) receptor antagonists plus dexamethasone have significantly improved the control of acute CINV, but delayed CINV remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have recently been approved for the prevention of both acute and delayed CINV. Palonosetron is a second-generation 5-HT(3) receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT(3) receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 (NK-1) receptor antagonists. Casopitant is another NK-1 receptor antagonist, which is under review by the US FDA after recent completion of phase III clinical trials. The introduction of these new agents has generated revised antiemetic guidelines for the prevention of CINV. Future studies may consider the use of palonosetron, aprepitant and casopitant with other antiemetic agents (e.g. olanzapine, gabapentin, cannabinoids) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

High incidence of Antiemetic treatment failure to standard chemotherapy in women with breast cancer – A prospective QOL study in clinical practice setting in Spain – EME-Q Study

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24 h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24–120 h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy–induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.