Mirogabalin vs pregabalin for chemotherapy-induced peripheral neuropathy in pancreatic cancer patients

Abstract Background The prognosis of pancreatic cancer (PC) has been improved by new chemotherapy regimens (combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP)). Unfortunately, chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of these two regimens. The efficacy of pregabalin for CIPN has been reported in previous studies. However, the efficacy of mirogabalin for CIPN remains unknown. Thus, in this study, we aimed to clarify which drug (mirogabalin or pregabalin) was more valuable for improving CIPN. Methods A total of 163 PC patients who underwent FOLFIRINOX or GnP between May 2014 and January 2021 were enrolled. Among them, 34 patients were diagnosed with CIPN. Thirteen patients were treated with mirogabalin (mirogabalin group), and twenty-one patients were treated with pregabalin (pregabalin group). Treatment efficacy was compared between the two groups. Results In both the mirogabalin group and the pregabalin group, the grade of patients with CIPN at 2, 4, and 6 weeks after the initiation of treatment showed significant improvement compared to the pretreatment grade. Notably, the rate of CIPN improvement was higher in the mirogabalin group than in the pregabalin group (2 weeks: 84.6% (11/13) vs 33.3% (7/21), P value = 0.005; 4 weeks, 6 weeks: 92.3% (12/13) vs 33.3% (7/21), P value = 0.001). Conclusions Although both mirogabalin and pregabalin were effective at improving CIPN, mirogabalin might be a suitable first choice for CIPN in PC patients. Trial registration Not applicable

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Efficacy of treatment of vulva cancer patients and analysis of their hormonal status.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21127 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21127-e21127

Author(s):

Galina A. Nerodo ◽

Ekaterina Nerodo

Keyword(s):

Positive Result ◽

Cancer Patients ◽

Treatment Efficacy ◽

Blood Concentration ◽

Hormonal Status ◽

Blood Concentrations ◽

Negative Results ◽

Group 2 ◽

Vulva Cancer ◽

Group 1

e21127 Background: hormonodependency of vulva is wellknown. This broughtusto study hormonal status of vulva cancer patients depending on treatment efficacy Methods: we present comparative analysis of hormonal status of vulva cancer patients in two groups: group 1 (50 patients) without relapse of the disease in 5-year period, and group 2 (35 patients) with relapse developed within the first year. Blood concentrations of testosterone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone were determined in all patients under study by means of radiometric methods. Estrone, estradiol, estriol with subsequent calculation of their sum were determined in daily urine by Brown method. Results: In the presence of effect (group 1) initial total amount of estrogens was twice as large than in its absence. In group 1 estradiol concentration exceeded the corresponding parameter of group 2 by three times(7.6±0.6 & 1,4±0.3,p<0.001). The amount of secreting estriol at positive result was almost twice higher than in cases of absence of the effect(10.02±1.7 & 4.6±0.49, p<0.001). The groups differed by secretion levels of follicle-stimulating and luteinizing hormones. Blood concentration of these hormones was lower in negative results that in positive. Distinct differences were also observed in progesterone and prolactin levels. In the group with positive result of treatment progesterone concentration was much higher than in the group without treatment effect. On the contrary, prolactin concentration in group 1 was significantly less than in group 2. The highest degree of reliability of quantitative indices related to treatment efficacy was observed for progesterone. Positive result of corresponding treatment may be predicted at normal initial progesterone level, and negative result at its low level (3-4 times lower than the norm). Another parameter - blood concentration of prolactin - can be used almost with the same degree of reliability. Conclusions: results of the study allow to suggest an existence of interrelation between treatment efficacy of vulva cancer patients and functional activity of hypophysis-gonadal system. Some of its parameters may be used to predict results of complex treatment of vulva cancer patients.

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Cobimetinib plus gemcitabine is an active combination in KRAS G12R-mutated in previously chemotherapy-treated and failed pancreatic patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4642 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4642-4642

Author(s):

Bach Ardalan ◽

Jared Addison Cotta ◽

Miriam Gombosh ◽

Jose Ignacio Azqueta

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Tumor Regression ◽

Mapk Pathway ◽

Progression Free Survival ◽

Mek Inhibitor ◽

Kras Mutations ◽

Positive Study ◽

Group 2 ◽

Group 1

4642 Background: he KRAS proto-oncogene is involved in the RAS/MAPK pathway. Various G12X mutations have been examined with the most common mutations being G12D (40%), G12V (30%), and G12R (15-20%) in pancreatic cancer patients. Throughout the course of studying the G12X mutations, we have observed that not all KRAS mutations are equal. Preclinical data shows G12R is impaired in pI3Kα signaling, as compared to KRAS G12V/D. This mechanism is important in PDAC as it allows tumor growth to be sustained. In preclinical studies, PDX derived tumors were transplanted in mice and were treated with a MEK inhibitor plus chemotherapy, which demonstrated a greater tumor regression than either agent alone. Therefore, we have decided to treat patients with Gemcitabine alongside a 2nd generation MEK inhibitor (Cobimetinib). Methods: In our single arm study, 13 KRAS mutated pancreatic patients (KRAS G12D, G12V, and G12R) received the combination of Cobimetinib 20mg BID weekly for three weeks alongside Gemcitabine at 1000mg/m2 weekly, followed by one week of rest. The above constitutes one cycle. Results: Patients were divided into two groups; Group 1 consists of seven patients that were KRAS G12D/G12V mutated, and Group 2 included six KRAS G12R mutated patients. In Group 1, seven patients on treatment progressed and died within two months on the study. In Group 2, one achieved PR and others stable disease. Median progression-free survival was 6.0 months (95% CI 3-9.3 months) and median OS has not been reached. All patients are alive at 8 months. Common adverse reactions include rash, fatigue, nausea, and vomiting. Cancer antigen 19-9 decreased in ≥ 50 of all patients in the latter group. We would like to report our positive study to the society. Moreover, we intend to confirm the study in a larger patient cohort. Conclusions: Pancreatic cancer patients that demonstrate KRAS G12R mutations are treatable with a new active combination chemotherapy.

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Risk Factors for Peripheral Neuropathy Induced by Albumin-bound Paclitaxel Plus Gemcitabine Therapy in Pancreatic Cancer Patients

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) ◽

10.5649/jjphcs.45.127 ◽

2019 ◽

Vol 45 (3) ◽

pp. 127-134

Author(s):

Naho Yamamoto ◽

Yuki Hori ◽

Rikako Takahiro ◽

Yukio Suga ◽

Tsutomu Shimada ◽

...

Keyword(s):

Risk Factors ◽

Pancreatic Cancer ◽

Peripheral Neuropathy ◽

Cancer Patients

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The effect of duloxetine on chemotherapy-induced peripheral neuropathy in advanced pancreatic cancer patients receiving gemcitabine plus nab-paclitaxel treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.453 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 453-453

Author(s):

Hidetaka Suzuki ◽

Akira Shinohara ◽

Izumi Ohno ◽

Shuichi Mitsunaga ◽

Misaki K Takeno ◽

...

Keyword(s):

Pancreatic Cancer ◽

Peripheral Neuropathy ◽

Cancer Patients ◽

Advanced Pancreatic Cancer ◽

Dose Intensity ◽

Cancer Center ◽

Once Daily ◽

Center Hospital ◽

Platinum Agents

453 Background: Recently, gemcitabine plus nab-paclitaxel (GN) has come to be used frequently as the first-line chemotherapy for advanced pancreatic cancer. It has been reported that chemotherapy-induced peripheral neuropathy (CIPN) associated with nab-paclitaxel (nab-PTX) may impair the quality of life of the patients, and may, moreover, necessitate dose reduction or early cessation of the chemotherapy, thereby potentially impacting patient survival. However, there are no established treatments against CIPN. Several reports have suggested that duloxetine, which has been proved to be highly effective in managing diabetic peripheral neuropathy, is also effective against CIPN induced by platinum agents and taxanes. The aim of this study was to examine the frequency of nab-PTX related CIPN, its various influences, and the efficacy of duloxetine in the management of CIPN. Methods: Data of 121 pancreatic cancer patients who received GN as first chemotherapy between December 2014 and December 2015 at the National Cancer Center Hospital East, Japan, were analyzed retrospectively. Results: The frequency of CIPN of any grade was 60.3% (73 patients) and that of CIPN of grade ≥ 2 was 21.5% (26 patients). Among the patients who showed CIPN, 34 patients received 20-60 mg of duloxetine once daily, and the remaining patients never received it (no duloxetine group). 18 patients were on duloxetine for more than four weeks (the duloxetine group). 8 patients discontinued duloxetine in less than four weeks because of its side effects, such as, nausea, and somnolence. In the duloxetine group, CIPN was improved in 4 patients, and remained non-progressive in 12 patients. The relative dose intensity (RDI) of nab-PTX since the emergence of CIPN in the duloxetine group was higher than that in the no duloxetine group (63.2 % vs. 48.2 %, p = 0.0046). Conclusions: The frequency of nab-PTX related CIPN at our hospital was almost similar to that of previous reports. The results of this study suggest the possibility that duloxetine not only improves nab-PTX-related CIPN, but delays its progression. Therefore, it might contribute to continuing GN with a high RDI for longer periods of time.

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