Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin.

1994 ◽  
Vol 12 (10) ◽  
pp. 2204-2210 ◽  
Author(s):  
R M Navari ◽  
H G Kaplan ◽  
R J Gralla ◽  
S M Grunberg ◽  
R Palmer ◽  
...  
Keyword(s):  
Vital Signs ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
First Episode ◽  
High Dose ◽  
Adverse Experiences ◽  
Major Response ◽  
Chemotherapy Patients ◽  
To Receive ◽  
Antiemetic Medication

PURPOSE To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS After granisetron doses of 5, 10, 20, and 40 micrograms/kg, a major response (< or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms/kg dosing groups than in the 5-micrograms/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION A single 10-, 20-, or 40-micrograms/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms/kg dose and the 20- and 40-micrograms/kg doses. Granisetron was well tolerated at all doses.

GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.

1989 ◽  
Vol 7 (6) ◽  
pp. 700-705 ◽  
Author(s):  
P J Hesketh ◽  
W K Murphy ◽  
E P Lester ◽  
D R Gandara ◽  
A Khojasteh ◽  
...  
Keyword(s):  
Response Rate ◽  
Complete Response ◽  
High Dose ◽  
Effective Agent ◽  
Acute Emesis ◽  
Major Response ◽  
Hepatic Transaminase ◽  
To Receive ◽  
Administration Schedules ◽  
Antiemetic Agents

We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin. Patients were evaluated for emetic episodes (vomiting or retching) over a 24-hour period following cisplatin. All patients were evaluable for toxicity and 83 were evaluable for efficacy. The overall antiemetic response rate was 75% (55% complete response [CR], 20% major response). No difference in antiemetic control between the two administration schedules was noted. Patients with histories of heavy ethanol use had significantly better antiemetic control (74% CR) than modest or non-drinkers (33% CR). Toxicity of GR 38032F was modest and independent of administration schedule. The most common adverse events included mild hepatic transaminase elevations, self-limited diarrhea, dry mouth, headache, and mild sedation. Our data indicate that GR 38032F is a safe and effective agent in the control of acute cisplatin-induced nausea and vomiting. Additional trials exploring dosing, schedule, and comparison to standard antiemetic agents are indicated.

High-dose intravenous metoclopramide versus combination high-dose metoclopramide and intravenous dexamethasone in preventing cisplatin-induced nausea and emesis: a single-blind crossover comparison of antiemetic efficacy.

1985 ◽  
Vol 3 (2) ◽  
pp. 245-251 ◽  
Author(s):  
S B Strum ◽  
J E McDermed ◽  
D F Liponi
Keyword(s):  
Patient Preference ◽  
Nausea And Vomiting ◽  
High Dose ◽  
Chemotherapy Response ◽  
Antiemetic Efficacy ◽  
Study Results ◽  
Nausea And Emesis ◽  
To Receive ◽  
Single Blind ◽  
Crossover Comparison

We tested the safety and antiemetic effectiveness of intravenous (IV) dexamethasone (DXM) as an adjunct to high-dose IV metoclopramide (MCP) to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy. Response was determined by using objective and subjective criteria. Thirty patients were randomly assigned to receive MCP alone at a dose of 2 mg/kg IV for three doses or the same dose of MCP plus 20 mg of DXM IV for three doses. Twenty evaluable patients received a second course of cisplatin and were crossed over to the opposite arm. Study results did not show a statistically significant advantage of combination MCP plus DXM over MCP alone using strict objective criteria for antiemetic response. However, patients subjectively preferred MCP plus DXM over MCP alone by nearly a 6:1 ratio, regardless of the randomization sequence. Although the addition of DXM does not appear to objectively improve emetic protection with high-dose MCP, we recommend MCP plus DXM to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy when the use of steroids is not contraindicated, in view of patient preference for the combination.

A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy.

1991 ◽  
Vol 9 (5) ◽  
pp. 721-728 ◽  
Author(s):  
J Hainsworth ◽  
W Harvey ◽  
K Pendergrass ◽  
B Kasimis ◽  
D Oblon ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Number ◽  
Chemotherapeutic Agents ◽  
Nausea And Vomiting ◽  
High Dose ◽  
Concurrent Administration ◽  
Major Response ◽  
Parallel Group ◽  
Blind Comparison ◽  
Single Blind

Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy.

Treatment of chemotherapy-induced breakthrough nauea and vomiting

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20536-e20536 ◽  
Author(s):  
R. M. Navari ◽  
S. E. Gray
Keyword(s):  
Serotonin Receptor ◽  
Rescue Therapy ◽  
Performance Status ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
Ecog Performance Status ◽  
Difficult Situation ◽  
Serotonin Receptor Antagonists ◽  
Drug Classes ◽  
To Receive

e20536 Background: Patients may experience breakthrough nausea and vomiting (BNV) despite adequate prophylaxis for chemotherapy-induced nausea and vomiting (CINV). BNV presents a difficult situation as treatment of ongoing nausea and vomiting is challenging. We investigated three different drug classes for the treatment of BNV: phenothiazines (prochlorperazine)(Pro), dopamine-serotonin receptor antagonists (metoclopramide) (Meto), and a corticosteroid-thiobenzodiazepine combination (dexamethasone plus atypical antipsychotic olanzapine) (Dex-Olan). Methods: Adult patients, receiving moderately emetogenic chemotherapy and CINV prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist and Dex pre-chemotherapy and Dex post-chemotherapy according to ASCO guidelines, who experienced BNV during the five days post-chemotherapy were randomized to receive Pro, 10 mg IV, and 10 mg, po, bid for three days; Meto, 20 mg IV, and 10 mg, po, bid for 3 days; or Dex, 20 mg IV and Olan, 5 mg, po, bid for three days. All patients also received at least one liter of IV fluids during the IV phase of their treatment. Patients were excluded if they had undergone rescue therapy with any of the study agents. Beginning with the first day of treatment for BNV (day 1) and daily through day 5, patients recorded episodes of vomiting/retching, nausea, other symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of any additional rescue therapy. One hundred six patients (median age 61, range 37 - 85, 60 males, ECOG performance status ≤ 2) consented to the protocol and 100 were evaluable. Results: A complete response (no emesis, no additional rescue) for the five days post-initiation of BNV treatment was recorded for 7 of 35 patients (20%) in the Pro regimen, 12 of 33 patients (36%) receiving the Meto regimen, and 21 of 32 patients (66%) receiving the Dex-Olan regimen. There were no Grade III or IV treatment related toxicities. Conclusion: The combination of Dex-Olan was an effective treatment for BNV and was significantly more effective than Pro or Meto alone. No significant financial relationships to disclose.

Preventive effect of rikkunshito, traditional Japanese medicine, for chemotherapy-induced nausea and vomiting.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 131-131
Author(s):  
Shinya Kajiura ◽  
Ayumu Hosokawa ◽  
Sohachi Nanjyo ◽  
Hiroki Yoshita ◽  
Nobuhiro Suzuki ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
High Dose ◽  
Preventive Effect ◽  
Major Toxicity ◽  
Traditional Japanese Medicine ◽  
Significant Difference ◽  
Anti Cancer ◽  
Cancer Anorexia

131 Background: Supportive therapies are being developed for chemotherapy-induced nausea and vomiting (CINV). Rikkunshito is a Kanpo medicine, which is a part of traditionally practiced Japanese-based ancient Chinese medicine. It has been reported to be effective against cisplatin-induced anorexia in rats. In the present study, we evaluated the preventive effect of Rikkunshito for CINV in patients receiving high-dose cisplatin. Methods: We selected subjects who received chemotherapy including cisplatin (≥60mg/m2) for gastric or esophageal cancer between April 2010 and August 2012 at our institution. We targeted 20 cases treated without a reduction in the anti-cancer medication in the second course and added 7.5g/day of Rikkunshito, orally administered for seven days, to their second course treatment regimen. All cases were treated with 5-HT3 receptor antagonist and steroid, and palonosetron for the prevention of CINV in their first and second courses. We evaluated the complete response (CR, defined as no emesis and no rescue medication) rate and other toxicity, according to CTCAE v4.0, of the first and second courses. Results: The median age of the patients was 63 years (range, 49–77 years). The chemotherapy regimens were cisplatin + 5-FU in 15 cases with esophageal cancer, cisplatin + S-1 in five cases with gastric cancer. Anorexia in the first course was grade 0/1/2 = 5/11/4, but had been mitigated in the second course to grade 0/1/2 = 12/6/2 (P = 0.042). CR rate was 75.0% in the first course (95% CI, 56.0%–94.0%) and by the second course had improved to 95.0% (95% CI, 85.4%–100%). And about the other major toxicity, there was no significant difference between first and second courses. Conclusions: These results suggest that Rikkunshito has the potential to improve CINV in patients receiving high-dose cisplatin.

Phase I/II study of oxaliplatin dose escalation via a laparoscopic approach using pressurized aerosol intraperitoneal chemotherapy (PIPOX trial) for nonresectable peritoneal metastases of digestive cancers (stomach, small bowel and colorectal).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15027-e15027 ◽  
Author(s):  
Frederic Dumont ◽  
Michele Boisdron-Celle ◽  
Sandrine Hiret ◽  
Helene Senellart ◽  
Judith Raimbourg ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Laparoscopic Approach ◽  
Complete Response ◽  
Minor Response ◽  
Major Response ◽  
Digestive Cancers ◽  
Grade 3 ◽  
Ecog Ps ◽  
To Receive

e15027 Background: The pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new route of intraperironeal drug administration that enhances the absorption of oxaliplatin. The objectives were to determine the MTD and PK of Oxaliplatin administred via the PIPAC technic. Methods: This was a phase I two center study with standard 3 x 3 design for pts with extended peritoneal carcinomatosis from gastrointestinal cancer (gastric PCI>4, small bowell PCI>13, colorectal PCI>15), ECOG PS≤1 and no organ dysfunction. The primary endpoint are dose determining dose limiting toxicity (DLT), maximum tolerable dose (MTD), recommandation dose for the phase 2 (RD2P) and PK of oxaliplatin. The dose escalation was in 50 mg/m2 steps up to a maximum of 300 mg/m² and starting with 90 mg/m². Pts were monitored for DLT from the first PIPAC up to 4-6 weeks after the second PIPAC. Each patient who experiences good tolerance will be invited to receive two to five PIPAC procedures at 4–6 week intervals. A systemic chemotherapy was allowed between the PIPAC session. Adverse event (AEs) were defined according NCI-CTCAE toxicity scale version 4. Results: To date, 10 patients received 31 PIPACs procedures and were treated in 2 differents dl. Two DLTs (grade 4 allergic reaction and grade 3 neutropenia) occurred at second level dose of 140 mg/m2 and no one at 90mg2. Frequent treatment related AE (TRAE) grade ≤ 2 during PIPACs sessions were nausea (9/31), abdominal pain (8/31) and fatigue (7/31). Nine patients were evaluable for response after at least 2 PIPACs. The histologic peritoneal regression grading score (PRGS) were 4 (no response), 3 (minor response), 2 (major response), and 1 (complete response) in respectively 0, 5, 2 and 2 pts. Pts with PRGS 1 underwent complete cytoreductive surgery and HIPEC. In this ongoing study, the PK profile is currently investigated. Conclusions: The RP2D of oxaliplatin during PIPAC was 90mg/m2 with correct tolerance and some patient have experienced of major histological response allowing a secondary complete resection. The study was opened for phase II enrollement. Clinical trials informations: NCT03294252 .

scholarly journals Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting

2020 ◽  
Vol 52 (3) ◽  
pp. 907-916 ◽  
Author(s):  
Jin Hyoung Kang ◽  
Jung Hye Kwon ◽  
Yun-Gyoo Lee ◽  
Keon Uk Park ◽  
Ho Jung An ◽  
...  
Keyword(s):  
Daily Life ◽  
Complete Response ◽  
Risk Difference ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Complete Protection ◽  
Highly Emetogenic Chemotherapy ◽  
Secondary Endpoints ◽  
To Receive

PurposeThe purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting. Materials and MethodsPatients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.ResultsA total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.ConclusionIn all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

scholarly journals S209. DRUG-NAïVE FIRST-EPISODE SCHIZOPHRENIA SPECTRUM DISORDERS: PHARMACOLOGICAL TREATMENT PRACTICES IN INPATIENT UNITS IN HUNAN PROVINCE, CHINA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S118-S118
Author(s):  
Mengran Zhu ◽  
Maria Ferrara ◽  
Wenjian Tan ◽  
Xingbo Shang ◽  
Sumaiyah Syed ◽  
...  
Keyword(s):  
Mental Health ◽  
Health Care ◽  
Mental Health Care ◽  
Hunan Province ◽  
First Episode ◽  
High Dose ◽  
Schizophrenia Spectrum ◽  
Drug Naïve ◽  
First Episode Schizophrenia ◽  
To Receive

Abstract Background Antipsychotics represent the core of treatment for first-episode schizophrenia (FES). The choice of the first antipsychotic in drug-naïve FES patients is delicate, as it could influence both adherence to medications and the course of the illness. In China, mental health care for schizophrenia is mainly provided by psychiatric hospitals, due to the limited resources in outpatient community care. Psychiatrists and nurses are the main providers of mental health care, and medication is becoming the primary intervention for mental illness. In 2015, the second edition of China’s Guidelines for Schizophrenia was released. The use of a minimum effective dose of a single antipsychotic has been indicated for FES, consistent with multiple international guidelines. Since the current treatment practice for FES in China is unknown, this study aimed to describe antipsychotic prescription patterns for drug-naïve FES inpatients, and factors associated with practices deviating from China’s current guidelines. Methods This was a retrospective study. Participants included all inpatients, ages 7 to 45 years, experiencing a first episode of schizophrenia-spectrum disorder with a duration of untreated illness (interval between onset of psychotic symptoms and first antipsychotic prescription) less than 18 months, admitted between Aug 1st,2016 and Aug 1st,2017 to one of eight hospitals in Hunan Province. Demographics, clinical characteristics, and prescriptions at discharge were collected from electronic medical records. Descriptive analysis was used to describe prescription patterns. Logistic regression and random forest methods were used to model relationships between factors and deviations from China’s guidelines. Results Of the 602 inpatients included in the study, 598(99.3%) were prescribed antipsychotics at discharge, mostly risperidone (41.8%) and olanzapine (41.0%). Polytherapy (being prescribed more than one antipsychotic) was present in 121 (20.2%) participants. The prescription rate of high-dose antipsychotics among adults was 32.9%, and of off-label antipsychotics among minors was 23.2%. Adults (OR=1.95, 95% CI: 1.14–3.34, compared to minors) and patients with longer length of stay (OR=1.09, 95% CI: 1.03–1.14) were more likely to receive polytherapy. Younger age (OR= 0.96, 95% CI 0.93–0.99), having non-tertiary hospitalization (OR=0.38, 95% CI 0.24–0.59, compared to tertiary hospitalization), and being prescribed polytherapy (OR= 3.56, 95% CI 2.17–5.86, compared to monotherapy) were associated with high-dose antipsychotics prescription. Participants younger than 13 were more likely to receive off-label antipsychotics. Clozapine was prescribed to 45 (7.5%) patients, and more frequently to those hospitalized in non-tertiary facilities (χ2= 8.606, P=0.003) and receiving polytherapy (χ2= 81.488, P&lt;0.001). Patients receiving clozapine had longer length of stay than those who did not (mean (SD): 8.02(4.93) vs 4.35(4.18) weeks, P&lt;0.001). Discussion Our study showed that most of the FES inpatients were prescribed antipsychotic in monotherapy, in compliance with current guidelines. Deviations from guidelines were found in younger patients with schizophrenia, and in clozapine prescriptions. Different practices were observed between tertiary and non-tertiary hospitals, suggesting possible challenges in delivering mental health care in those facilities where disproportionate distribution of resources might happen. Given the ongoing implementation of the National Mental Health Working Plan, these results provide a useful representation of the current practice in China and could help decision-makers on resource allocation in order to promote the best treatment for first-episode psychosis.

Randomized double-blind evaluation of dronabinol for the prevention of chemotherapy-induced nausea.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9061-9061
Author(s):  
Steven M. Grunberg ◽  
Mark F. Munsell ◽  
Phuong Khanh H. Morrow ◽  
Jeffrey Kent Giguere ◽  
Ulla Jo Ule ◽  
...  
Keyword(s):  
Complete Response ◽  
Double Blind ◽  
Mood Changes ◽  
Significant Difference ◽  
P 16 ◽  
Chemotherapy Patients ◽  
Age Range ◽  
To Receive ◽  
Made In ◽  
Antiemetic Agents

9061 Background: Although great progress has been made in the control of chemotherapy-induced vomiting (CIV), prevention of chemotherapy-induced nausea (CIN) has been less successful. Preliminary data suggests that some families of lesser used antiemetic agents, such as the cannabinoids, may have greater efficacy against nausea than against vomiting. Methods: Adult solid tumor patients (pts) receiving cyclophosphamide ≤ 1500 mg/m2 (C) and/or doxorubicin ≥ 40 mg/m2 (A) were eligible. Pts could have received prior mildly emetogenic chemotherapy (EC). Pts were not eligible who were receiving other moderately or highly EC, were receiving cranial, abdominal or pelvic radiotherapy, had CIV/CIN with previous chemotherapy, had other causes for nausea/vomiting besides chemotherapy, or were scheduled to receive other antiemetics. Pts with habitual cannabinoid use were not eligible. All pts received palonosetron 0.25 mg (PALO) and dexamethasone 10 mg (DXM) IV before chemotherapy. Patients were randomized double-blind to receive dronabinol 5 mg (D) or matching placebo (P) 3 times a day for 5 days. Nausea, vomiting and toxicity data was collected daily for 5 days. Results: 62 pts were entered on study – female/male 61/1, White/Black/Hispanic/Other 45/14/2/1, median age (range) 58 (29-76). No significant difference was noted in CIV-dependent endpoints (including No Vomiting, Complete Response, or Complete Protection) or in rescue medication use. However pts receiving D had a shorter duration of nausea – Mean number of days of nausea (D vs P) 1.86 days vs 3.10 days (p=0.027) – and a trend toward greater frequency of No Nausea (D vs P) 37% vs 17% (p=0.143). Common toxicities included fatigue (D/P 17/11), headache (D/P 16/16), dizziness (D/P 14/7), constipation (D/P 14/11), and diarrhea (D/P 13/6) No pt discontinued therapy due to mood changes. Conclusions: Low-dose D decreased the duration of CIN and increased the frequency of No Nausea in pts receiving C and/or A. Agents to prevent CIV (such as PALO and DXM) and to prevent CIN (such as D) have complementary activity and result in improved overall control when used together.

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT): Long-term efficacy and safety outcomes.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 328-328
Author(s):  
Andrea Necchi ◽  
Luigi Mariani ◽  
Nicola Nicolai ◽  
Daniele Raggi ◽  
Elena Farè ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Germ Cell Tumors ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose ◽  
Conventional Dose ◽  
Unselected Patient ◽  
Major Response ◽  
Grade 3

328 Background: Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. Methods: We retrieved data of pts who received ifosfamide at 2.5 gr/m2 (with mesna) on days 1-2, etoposide and cisplatin at 100 mg/m2 and 33 mg/m2, respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. Results: From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm- were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP>1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. Conclusions: Dose-modified Italian PEI showed activity comparable with the best ones achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT.

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