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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.
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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.
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Mannitol for the prevention of cisplatin-induced nephrotoxicity: A retrospective comparison of hydration plus mannitol versus hydration alone in inpatient and outpatient regimens at a large academic medical center.
Williams, RP, Ferlas, BW, Morales, PC, Kurtzweil, AJ
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2017;(6):422-428
Abstract
Background Cisplatin-induced nephrotoxicity is a dose limiting adverse effect that occurs in nearly one-third of patients. Mannitol administration has been used as a means to negate this toxicity. Data regarding the efficacy of mannitol use in this context are conflicting and limited. Objective The aim of this study is to evaluate the effect of mannitol on renal function and describe the incidence of cisplatin-induced nephrotoxicity. Methods This study is a quasi-experimental retrospective analysis approved by the Institutional Review Board of inpatient and outpatient adults receiving cisplatin doses ≥40 mg/m2. The primary outcome was mean change in serum creatinine from baseline. Secondary outcomes included incidences of various grades of nephrotoxicity. Results A total of 313 patients (95 treated with mannitol and 218 without) were evaluated. The average increase in serum creatinine (mg/dL) was lower in patients who received mannitol versus those who did not (0.30 vs. 0.47; 95% confidence interval for difference, 0.03 to 0.31; P = 0.02). Grade 2 or higher nephrotoxicity occurred less frequently in patients who received mannitol versus those who did not (8% vs. 17%; P = 0.04). Non-gynecologic regimens and those who received doses ≥70 mg/m2 of cisplatin had lower rates of grade 2 or higher nephrotoxicity with mannitol (6% vs. 23%; P = 0.001, and 7% vs. 22%; P = 0.03, respectively). Conclusion The use of mannitol reduces the incidence and severity of nephrotoxicity in patients treated with cisplatin. The results of the study suggest mannitol may be most effective when used with non-gynecologic regimens and with cisplatin doses ≥70 mg/m2.
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Efficacy of mannatide combined with sodium cantharidate vitamin B6 in the treatment of malignant pleural effusions.
Wang, LZ, Zhang, HJ, Song, J
Asian Pacific journal of cancer prevention : APJCP. 2015;(9):3913-6
Abstract
OBJECTIVE To evaluate the efficacy of mannatide combined with sodium cantharidate vitamin B6 in the treatment of malignant pleural effusions. MATERIALS AND METHODS Data for 69 patients with malignant pleural effusions who did not receive systemic chemotherapy were collected. Injection into the thorax using mannatide combined with sodium cantharidate vitamin B6 was performed for 37 patients in the experimental group and mannatide combined with cisplatin for 32 patients in the control group. Objective responses, KPS (Karnofsky Scoring) and incidences of side effects between the two groups were compared. RESULTS 13 patients reached CR (complete response) and 11 PR (partial response) in the experimental group, while 12 patients reached CR and 9 PR in the control group, the difference in overall objective responses between the two groups not being significant (66.7% vs 63.6%, p=0.806). However, improvement of KPS in the experimental group was greater than in the control group; total side-effect incidences during the period of treatment were 22.2% (8/36) and 54.5% (18/33), respectively (p=0.006). CONCLUSIONS Regimen of mannatide combined with sodium cantharidate vitamin B6 had better improvement in quality-of-life and symptom relief, with a lower side-effect incidence in treatment of malignant pleural effusions.
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Randomized cross-over trial comparing inpatient and outpatient administration of high-dose cisplatin.
Cox, KM, Goel, S, O'Connell, RL, Boyer, M, Beale, PJ, Simes, RJ, Stockler, MR
Internal medicine journal. 2011;(2):172-8
Abstract
BACKGROUND/AIMS: Treatment with high-dose cisplatin (HDC) previously required inpatient (IP) admission with overnight hospitalization, but recently practice has shifted to outpatient (OP) therapy. We aimed to determine whether it is preferable to give HDC as an IP or OP using a two-period cross-over trial. METHODS Eligible patients were starting chemotherapy with ≥2 cycles of HDC (≥100 mg/dose) and were suitable for OP treatment. All patients received an IP cycle and OP cycle: the order was randomly allocated. Pre-hydration, anti-emetics and chemotherapy were identical for IP and OP. Post-hydration varied by group (3 L normal saline (NS) for IP, 2 L NS for OP). The primary outcome was patient preference for IP versus OP treatment. Secondary outcomes included aspects of health-related quality of life, adverse events (dose delays and reductions, elevated creatinine and unplanned readmissions) and resource use. RESULTS Fifty-nine patients were randomized, 53 completed two cycles of HDC. Most patients preferred OP treatment (36 vs 13, P = 0.002). There were no significant differences in patients' ratings of nausea, vomiting, fatigue, anxiety, depression or overall quality of life. Adverse events were few and unrelated to IP versus OP treatment. Nursing time was longer for IP than OP (163 vs 104 min, P < 0.001). CONCLUSION OP treatment was preferred by most patients, appeared safe and used less resources.
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Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).
Dietz, A, Rudat, V, Dreyhaupt, J, Pritsch, M, Hoppe, F, Hagen, R, Pfreundner, L, Schröder, U, Eckel, H, Hess, M, et al
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2009;(8):1291-300
Abstract
A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.
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Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study.
Moore, DH, Blessing, JA, McQuellon, RP, Thaler, HT, Cella, D, Benda, J, Miller, DS, Olt, G, King, S, Boggess, JF, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;(15):3113-9
Abstract
PURPOSE To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.
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Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells.
Holzer, AK, Katano, K, Klomp, LW, Howell, SB
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004;(19):6744-9
Abstract
PURPOSE Cisplatin (DDP)-resistant cells commonly exhibit reduced drug accumulation. Previous studies have shown that the major copper (Cu) influx transporter CTR1 controls the uptake of DDP in yeast and mammalian cells. The goal of this study was to examine the effect of Cu and DDP on the level and subcellular localization of hCTR1 protein in human ovarian carcinoma cells. EXPERIMENTAL DESIGN Cultured human ovarian carcinoma A2780 cells were exposed to DDP and Cu, and the effect on hCTR1 was determined using Western blot analysis and confocal digital deconvolution microscopy. RESULTS Loss of hCTR1 was triggered by DDP exposure in a concentration and time-dependent manner. Exposure to 0.5 micromol/L DDP for 5 minutes reduced hCTR1 levels and exposure to DDP concentrations > or =2 micromol/L caused almost complete disappearance. The loss of hCTR1 was observed within 1 minute of the start of exposure to 2 micromol/L DDP. Treatment of cells with 100 micromol/L Cu for 5 minutes produced a smaller effect. Pretreatment of cells with 2 micromol/L DDP for 5 minutes resulted in a 50% decrease in 64Cu uptake, demonstrating that the DDP-induced loss of hCTR1 detected by Western blot analysis and imaging was functionally significant. CONCLUSIONS DDP down-regulated the amount of its major influx transporter in cultured human ovarian carcinoma cells in a concentration- and time-dependent manner. The effect was observed at DDP concentrations within the range found in the plasma of patients being treated with DDP, and it occurred very quickly relative to the half-life of the drug.
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Cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) is more active than 5-fluorouracil, doxorubicin and methotrexate (FAMTX) in advanced gastric carcinoma.
Cocconi, G, Carlini, P, Gamboni, A, Gasperoni, S, Rodinò, C, Zironi, S, Bisagni, G, Porrozzi, S, Cognetti, F, Di Costanzo, F, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2003;(8):1258-63
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Abstract
BACKGROUND 5-Fluorouracil (5-FU), doxorubicin and methotrexate (FAMTX) and cisplatin, epirubicin, leucovorin and 5-FU (PELF) have both been reported to be superior to the combination 5-FU, doxorubicin and mitomycin C (FAM) in advanced gastric carcinoma. On the basis of the presence and dose intensity of the included agents, we hypothesised that PELF would be superior to FAMTX. PATIENTS AND METHODS Two hundred patients with untreated advanced gastric carcinoma were randomised to receive PELF or FAMTX for a maximum of six cycles or until disease progression. RESULTS The complete response (CR) rates to PELF and FAMTX were, respectively, 13% [95% confidence intervals (CI) 6% to 20%] and 2% (95% CI 0% to 5%; P = 0.003), and the objective response rates [CR plus partial response (PR) rates] 39% (95% CI 29% to 49%) and 22% (95% CI 13% to 30%; P = 0.009), thus significantly favouring the PELF combination. The survival rates after 12 months (30.8% versus 22.4%) and 24 months (15.7% versus 9.5%) were also higher among patients receiving PELF, but these differences were not statistically significant. The toxicities were qualitatively different but quantitatively similar. Both regimens seem to be feasible provided that careful patient monitoring is assured. CONCLUSIONS PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting.
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Enhanced effectiveness of last generation antiblastic compounds vs. cisplatin on malignant pleural mesothelioma cell lines.
de Cupis, A, Semino, C, Pirani, P, Loprevite, M, Ardizzoni, A, Favoni, RE
European journal of pharmacology. 2003;(2-3):83-95
Abstract
The purpose of this study was to examine the antiproliferative potentialities of a pool of new generation compounds (Paclitaxel, Docetaxel, Gemcitabine, Topotecan, SN-38) together with fenretinide, a synthetic derivative of retinoic acid, in comparison with the current first choice treatment cisplatin molecule, on a pool of human malignant pleural mesothelioma cell lines derived from either bioptic and pleural effusions samples. To evaluate the chemosensitivity features of malignant mesothelioma cells in vitro, we resorted to a rapid and reproducible colorimetric assay, a useful widely recognized tool for preclinical drug screening. In addition, by DNA content analysis and cellular morphologic assessment, we focused on the apoptosis as a potential mechanism of drug activity. The main results clearly indicate that, in all the models of malignant mesothelioma we handled in vitro, each tested antineoplastic agent is more powerful than cisplatin in inhibiting cell proliferation. Moreover, on experimental evidences basis, we can assume that the cytotoxic activity of tested compounds could be related, at least partially, to the drug-induced programmed cell death. This experimental study gives substance to the expected pharmacologic worth of the second generation antineoplastic drugs even if, in order to afford the most satisfactory biopharmacological approach, allowing to bypass the refractoriness to chemotherapy of this highly lethal tumour, further investigations at preclinical level are required.