-
1.
Neutropenic sepsis rates in patients receiving bleomycin, etoposide and cisplatin chemotherapy using olanzapine and reduced doses of dexamethasone compared to a standard antiemetic regimen.
Gjafa, E, Ng, K, Grunewald, T, Galazi, M, Skyllberg, E, Wilson, P, Alifrangis, C, Shamash, J
BJU international. 2021;(2):205-211
Abstract
OBJECTIVE To investigate whether the use of a steroid-sparing antiemetic protocol (substituting dexamethasone with olanzapine) affects the incidence of neutropenia and associated hospital admissions in patients receiving bleomycin, etoposide and cisplatin (BEP) chemotherapy. PATIENTS AND METHODS Records from 108 patients who received BEP at St Bartholomew's Hospital, London were divided into two groups according to antiemetic regimen. Group 1 (treated 2008-2013) were treated with a steroid-containing antiemetic protocol and group 2 (treated 2014-2017) were treated according to a steroid-sparing protocol, i.e. using olanzapine. Outcomes included incidence of neutropenia at nadir blood count, severity of neutropenia, hospital admissions attributable to febrile neutropenia (FN) and baseline risk factors associated with FN. Statistical analyses were performed using two-sided chi-squared tests. RESULTS The baseline characteristics of the two groups were balanced with regard to age, gender, histology, and proportion of patients with International Germ Cell Cancer Collaborative Group poor-risk disease. The incidence of neutropenia of any grade (group 1, 96.2%; group 2, 98.1%) was similar, although group 2 had more patients with severe neutropenia than group 2 (77.7% vs 88.8%). There was a significant difference in FN incidence (group 1, 22%; group 2 7.5%; P = 0.030). Most cases of FN occurred in cycle 1. Two baseline characteristics were over-represented in patients who developed FN: female sex and age ≥50 years. CONCLUSION By comparing two cohorts who received prophylactic antibiotics, our audit suggests that rates of FN-related admissions were lower in the cohort of patients in whom we employed a steroid-sparing antiemetic protocol.
-
2.
Randomized study comparing mannitol with furosemide for the prevention of cisplatin-induced renal toxicity in non-small cell lung cancer: The OLCSG1406 trial.
Makimoto, G, Hotta, K, Oze, I, Ninomiya, K, Nakanishi, M, Hara, N, Kano, H, Watanabe, H, Hata, Y, Nishii, K, et al
Asia-Pacific journal of clinical oncology. 2021;(1):101-108
Abstract
AIM: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer. METHODS Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. RESULTS The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival. CONCLUSION The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations.
-
3.
Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy.
Yoshiya, T, Mimae, T, Ito, M, Sasada, S, Tsutani, Y, Satoh, K, Masuda, T, Miyata, Y, Hattori, N, Okada, M
Investigational new drugs. 2020;(2):485-492
Abstract
Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.
-
4.
A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer.
Rolland, V, Meyer, F, Guitton, MJ, Bussières, R, Philippon, D, Bairati, I, Leclerc, M, Côté, M
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 2019;(1):4
Abstract
BACKGROUND Cisplatin-induced hearing loss is frequent and severe. Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. METHODS Eligible participants were newly diagnosed patients with stage III or IV squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or larynx and scheduled to be treated by concurrent chemoradiation (CCR). Patients with asymmetric hearing were not eligible. The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43. A baseline pre-treatment complete audiometric evaluation (pure tone at frequencies ranging from 0.5 to 14 kHz, bone conduction at 0.5-4 kHz and DPOAEs) was performed. Adverse effects were noted according to CTCAE. On the day before the beginning of CCR, eligible and consenting patients were randomized to receive a trans-tympanic injection of the gel either in the left ear or in the right ear. A final post-treatment complete audiometric evaluation was scheduled to be performed 1 month after the end of CCR by audiologists kept blind to the ear assignment. For the main outcome, the permanent threshold shift (PTS) in decibel (dB) was calculated as the difference between the final and baseline measures at all pure tone frequencies at 0.5-14 kHz for each patient and for each ear. The main outcome was assessed blindly in a mixed linear model with the PTS as the dependent variable and intervention, frequency, their interaction and radiation dose to the cochlea as independent variables. RESULTS Between January 2015 and April 2016, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. CONCLUSIONS Our trial suggests that STS deposited on the round window was safe for the middle and inner ears. More work is needed to improve the efficacy of trans-tympanic injections of cisplatin antidotes. TRIAL REGISTRATION ClinicalTrials.gov, NTC02281006 , Registered 3 November 2014.
-
5.
Effects of Reduction in Tumor Burden on Survival in Epithelioid Malignant Pleural Mesothelioma.
Mansfield, AS, Peikert, T, Vogelzang, NJ, Symanowski, JT
Mayo Clinic proceedings. 2018;(8):1026-1033
-
-
Free full text
-
Abstract
OBJECTIVE To understand the relationship between response and survival in malignant pleural mesothelioma (MPM). PATIENTS AND METHODS The original clinical trial was conducted from April 1999 through March 2001. Patients with epithelioid MPM (n=305) were categorized using modified pleural Response Evaluation Criteria in Solid Tumors by whether they responded to treatment. Median progression-free survival (PFS) and overall survival (OS) were estimated and hazard ratios for responders and nonresponders were estimated and compared using the log-rank test. Multivariable Cox proportional hazards models were used to adjust for baseline prognostic factors. RESULTS Patients who responded to frontline therapy had a significantly longer OS (hazard ratio, 0.34; 95% CI, 0.24-0.49; median, 20.6 months; 95% CI, 15.3 months to not reached) than did those who did not respond (median, 9.4 months; 95% CI, 8.1-11.0 months) (P<.001). Similarly, responders had a significantly longer PFS (hazard ratio, 0.50; 95% CI, 0.39-0.64; median, 7.8 months; 95% CI, 6.5-8.5 months) than did nonresponders (median, 3.7 months; 95% CI, 2.9-4.3 months) (P<.001). These results were confirmed when adjusting for baseline prognostic factors. We also observed a survival benefit associated with disease stabilization in MPM. CONCLUSION Our findings indicate that reduction in tumor burden or disease stabilization determined using modified pleural Response Evaluation Criteria in Solid Tumors is strongly associated with OS and PFS in epithelioid MPM.
-
6.
Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol.
Makimoto, G, Ichihara, E, Hotta, K, Ninomiya, K, Oze, I, Minami, D, Ninomiya, T, Kubo, T, Ohashi, K, Tabata, M, et al
Acta medica Okayama. 2018;(3):319-323
Abstract
Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration.
-
7.
The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.
Inoue, T, Takagi, H, Owada, Y, Watanabe, Y, Yamaura, T, Fukuhara, M, Muto, S, Okabe, N, Matsumura, Y, Hasegawa, T, et al
Trials. 2017;(1):485
Abstract
BACKGROUND Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. METHODS/DESIGN This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. DISCUSSION This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. TRIAL REGISTRATION Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.
-
8.
Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial.
Ikeda, M, Shimizu, S, Sato, T, Morimoto, M, Kojima, Y, Inaba, Y, Hagihara, A, Kudo, M, Nakamori, S, Kaneko, S, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2016;(11):2090-2096
-
-
Free full text
-
Abstract
BACKGROUND Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.
-
9.
Weekly versus Three-Weekly Cisplatin-based Concurrent Chemoradiotherapy as definitive treatment in Head and Neck Cancer- Where do we stand?
Rawat, S, Srivastava, H, Ahlawat, P, Pal, M, Gupta, G, Chauhan, D, Tandon, S, Khurana, R
The Gulf journal of oncology. 2016;(21):6-11
Abstract
PURPOSE To compare toxicity, compliance, and early response of weekly and 3-weekly cisplatin administration concurrent with radiotherapy as definitive treatment in locally advanced squamous cell carcinoma head and neck. MATERIALS AND METHODS Patients with histologically proven stage III - IV B head and neck carcinoma presenting from June 2013 to March 2014 were randomly assigned to weekly (35 mg/m2, 6 cycles; arm A) and 3 weekly (100 mg/m2, 3 cycles; arm B) cisplatin with concurrent radiotherapy. RESULTS 60 patients were randomly assigned to treatment, 30 in each arm. Median follow-up was 8 months (range 4-13). There was no significant difference in grade 3 mucositis between the two arms (75.9% vs 70%, p = 0.20). Grade 3 neutropenia was more frequent in arm B (55.2% vs 26.7%, p = 0.01). Hypomagnesemia was the commonest electrolyte imbalance and it was significantly higher in arm B (60% vs 20%, p = 0.001). Completion rate of scheduled chemotherapy cycles was higher for patients receiving weekly regimen. Response at 3 months was similar for all the patients {Complete Response (66.7% vs 62.1%), p = 0.200}. Our data suggested that there is a reduced need of hospitalization and supportive care measures for patients receiving weekly cisplatin with RT (p = 0.05). CONCLUSIONS Weekly cisplatin 35 mg/m2 chemotherapy concurrent with radiotherapy is equally effective and less toxic in terms of neutropenia, hypomagnesemia and need for supportive measures than the conventional 3 weekly cisplatin 100 mg/m2 regimen.
-
10.
Chemotherapy-induced nausea and vomiting: incidence and characteristics of persistent symptoms and future directions NCCTG N08C3 (Alliance).
Kottschade, L, Novotny, P, Lyss, A, Mazurczak, M, Loprinzi, C, Barton, D
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2016;(6):2661-7
-
-
Free full text
-
Abstract
BACKGROUND Despite newer agents, chemotherapy-induced nausea and vomiting (CINV) continues to remain a distressing side effect to a proportion of patients undergoing systemic anti-cancer therapy. METHODS We recently performed an unplanned secondary analysis on a previously reported negative phase III trial (N08C3) looking at the efficacy of gabapentin/placebo in combination with dexamethasone and a 5HT3 receptor antagonist in the prevention of CINV for 413 patients undergoing regimens with highly emetogenic chemotherapy (HEC). In the current study, we attempted to better understand the higher than expected rate of overall patient satisfaction, despite a low complete response rate in both arms. Additionally, we looked at patient variables and their relationship to rates of CINV. RESULTS Approximately one third of patients experienced more than mild nausea and reported scores on the Functional Living Index-Emesis that indicated interference with activities. Thirty-five percent reported nausea greater than 2.5 on a scale of 0 to 10 (0 being none), 19 % reported at least one emetic episode, and 49 % reported taking rescue medication. Nausea and vomiting on day 1, cisplatin therapy, and history of motion sickness significantly predicted delayed CINV. Age, combination chemotherapy (HEC with moderately emetogenic), and getting treatment for breast cancer predicted CINV on day 1. DISCUSSION These data confirm previous reports that subgroups of patients may be more prone to acute and delayed CINV. Future CINV study design may benefit from a more individualized approach to CINV management, targeting those patients who are truly at risk for CINV despite continued drug development efforts.