taxane and Genital-Neoplasms--Female

This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.. Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables.. Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p > 0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p < 0.001).. Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Case-Control Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Female; Genital Neoplasms, Female; Humans; Peripheral Nervous System Diseases; Pharmacogenetics; Prospective Studies; Taxoids

Lafutidine, an antagonist of histamine H2-receptor, has gastroprotective activity associated with activation of capsaicin-mediated sensory nerves. The objective of this study was to investigate the efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy in patients with gynecological malignancies.. Twenty patients with taxane-induced peripheral neuropathy during the treatment of gynecological malignancy were enrolled in this study. After obtaining their informed consent, lafutidine (20mg per day) was administered orally, the efficacy of which was assessed according to the Patient Neurotoxicity Questionnaire item 1.. Significant, moderate, slight, and no effects were observed in four, five, five, and six patients, respectively. The efficacy including significant and moderate effect was observed in nine (45%) of the 20 patients (95% confidence interval, 25.8%-65.8%). No adverse effects due to lafutidine were observed.. This pilot study supports the relatively high efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy. Further prospective studies are warranted.

Topics: Acetamides; Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Female; Genital Neoplasms, Female; Histamine H2 Antagonists; Humans; Middle Aged; Peripheral Nervous System Diseases; Piperidines; Pyridines; Taxoids

To assess the reproducibility of intrinsic relaxivity and both relaxivity- and susceptibility-based dynamic contrast enhanced (DCE) MRI in pelvic tumors; to correlate kinetic parameters obtained and to assess whether acute antivascular effects are seen in response to cisplatin- or taxane-based chemotherapy.. T1-weighted and T2*-weighted DCE-MRI and basal R2* measurements were performed on three consecutive days in women with gynecological tumors. The third scan was 21.0 (range 17.3-23.5) hours after the first cycle of chemotherapy. Kinetic parameter estimates were obtained and correlated between techniques. Test-retest reproducibility and response to treatment were assessed.. Relative blood volume (rBV) and relative blood flow (rBF) correlated strongly with transfer constant (Ktrans), kep, and the initial area under the gadopentetate dimeglumine (Gd-DTPA) concentration-time curve (IAUGC) (all P<0.01). The group 95% confidence interval (CI) for change was -10.8 to +12.1%; +/-5.1%; -9.5 to +10.5%; +/-7.5%; for Ktrans, ve, kep, and IAUGC, respectively, and +/-13.6%, +/-2.4%, +/-11.6%, and +/-11.0%, for rBV, mean transit time (MTT), rBF, and R2*, respectively. There were no significant acute changes in kinetic parameter estimates in response to treatment on group analysis, apart from a small decrease in ve.. The results confirm the dominant influence of flow on Ktrans in untreated gynecological tumors. There is no evidence of an acute, large magnitude antivascular effect caused by cisplatin- or taxane-based chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Female; Genital Neoplasms, Female; Humans; Magnetic Resonance Imaging; Middle Aged; Pelvic Neoplasms; Platinum; Regional Blood Flow; Reproducibility of Results; Taxoids

To identify genetic variants associated with chemotherapy-induced peripheral neuropathy (CIPN) symptoms among gynecologic cancer survivors and determine the variants' predictive power in addition to age and clinical factors at time of diagnosis.. Participants of a prospective cohort study on gynecologic cancers provided a DNA saliva sample and reported CIPN symptoms (FACT/GOG-Ntx). Genotyping of 23 single nucleotide polymorphisms (SNPs) previously identified as related to platinum- or taxane-induced neuropathy was performed using iPLEX Gold method. Risk allele carrier frequencies of 19 SNPs that passed quality checks were compared between those with/without high CIPN symptoms using logistic regression, adjusting for age. Receiver operating characteristic (ROC) curves using clinical risk factors (age, diabetes, BMI, Charlson Comorbidity Index, previous cancer diagnosis) with and without the identified SNPs were compared.. 107 individuals received platinum or taxane-based chemotherapy and provided sufficient DNA for analysis. Median age was 65.1 years; 39.6% had obesity and 8.4% diabetes; most had ovarian (58.9%) or uterine cancer (29.0%). Two SNPs were significantly associated with high CIPN symptomatology: rs3753753 in GPX7, OR = 2.55 (1.13, 5.72) and rs139887 in SOX10, 2.66 (1.18, 6.00). Including these two SNPs in a model with clinical characteristics led to an improved AUC for CIPN symptomatology (0.65 vs. 0.74, p = 0.04).. Genetic and clinical characteristics were predictive of higher CIPN symptomatology in gynecologic cancer survivors, and combining these factors resulted in superior predictive power compared with a model with clinical factors only. Prospective validation and assessment of clinical utility are warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cancer Survivors; Cohort Studies; Female; Genetic Predisposition to Disease; Genetic Variation; Genital Neoplasms, Female; Humans; Middle Aged; Organoplatinum Compounds; Peripheral Nervous System Diseases; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prospective Studies; Taxoids

Peripheral neuropathy is a common complication of cancer treatment impairing quality of life and function. This study explored the impact of a complementary and integrative medicine (CIM) program on taxane-induced peripheral neuropathy (TIPN).. Taxane-treated female patients with breast and gynecological cancer reporting TIPN-related symptoms were referred to an integrative physician, followed by patient-tailored CIM treatments (acupuncture with/without other modalities). Assessment of study outcomes at 6 to 12 weeks was conducted using the Measure Yourself Concerns and Wellbeing, which documented free-text narratives about patients' experience during the CIM treatment process. Content was analyzed using ATLAS.Ti software.. Of the 125 patients treated with taxanes, 69 had been referred for CIM treatment of TIPN-associated symptoms. Multidisciplinary narrative analysis identified 2 groups of CIM-treated patients: those with an apparently moderate improvement in symptoms (n = 35) and those with either only an apparent mild or no improvement at all. For 10 patients, assessment of their response to treatment was unclear. The 2 identified groups had similar demographic, cancer-related, and quality of life-related parameters at baseline. Content analysis of patients with an apparent moderate improvement suggested a short-term (24-48 hours) effect with acupuncture treatment, either alone or combined with manual, mind-body, and anthroposophic music therapies. Symptoms showing improvement included paresthesia and numbness.. Acupuncture and other CIM therapies may result in a short-term and transitory reduction in TIPN-related symptoms.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Complementary Therapies; Female; Genital Neoplasms, Female; Humans; Integrative Medicine; Middle Aged; Peripheral Nervous System Diseases; Precision Medicine; Taxoids

Taste disturbance is known to occur as one of the adverse events associated with chemotherapy for gynecological cancer, but few studies have attempted to assess it in practical terms. Therefore, a range of taste tests was performed in gynecological cancer patients.. The patients were 23 women with gynecological cancer being treated with anticancer agents. Subjective symptoms of altered taste were classified, and objective findings were obtained with the following four gustatory tests: serum trace element (zinc, copper, iron) levels, tongue cultures, electrogustometry, and the filter paper disc tests.. Of the 23 subjects, 11 perceived taste disturbances. The serum zinc level was consistently below the lower limit of normal. On tongue cultures, indigenous bacteria were seen in all patients during the entire treatment period. Electrogustometry revealed a tendency for the development of hypogeusia in the chorda tympani nerve field. Conversely, hypergeusia tended to develop gradually in the greater petrosal nerve field. The filter paper disc test revealed a tendency for the development of hypergeusia for sweetness, saltiness, and sourness in the chorda tympani nerve field. Hypogeusia for bitterness tended to develop with increasing number of chemotherapy cycles. The glossopharyngeal nerve field exhibited the same tendencies as observed in the chorda tympani nerve field. In the greater petrosal nerve field, there was a tendency for the development of hypergeusia for sweetness, sourness, and bitterness.. Abnormal test results were seen in half of patients after cancer chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Copper; Female; Genital Neoplasms, Female; Humans; Iron; Middle Aged; Taste Disorders; Taxoids; Tongue; Zinc

Chemotherapy-related hypersensitivity reaction seems to be problematic in the safe management of chemotherapy. In this study we investigated chemotherapy-related hypersensitivity reaction in patients with gynecologic malignancy.. Between January 2009 and December 2010, we examined hypersensitivity reaction (> or = grade2) using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. We analyzed the incidence, clinical features, management, and outcome.. We administered over 1,057 infusions (24 regimens) to 205 patients. We found a total of four hypersensitivity reactions (> or = grade 2) cases (carboplatin: 2; nedaplatin: 1; docetaxel: 1). Signs and symptoms were varied. In two cases, the same regimen was rechallenged by using anti-allergic drugs. The docetaxel case was successful. The carboplatin case was not successful.. Chemotherapy-related hypersensitivity reaction (> or = grade2) does not occur frequently. In the case of platinum, especially, carboplatin, re-administering after hypersensitivity reaction should be done carefully though platinum is a key drug in patients with gynecologic malignancies.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Carboplatin; Drug Hypersensitivity; Female; Genital Neoplasms, Female; Humans; Japan; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Taxoids; Young Adult

There are extremely limited data available in the general oncology or gynecologic cancer literature to document the effectiveness of antiemetic therapy over multiple courses of cytotoxic chemotherapy.. To examine this highly clinically relevant issue, we analyzed the complete treatment course of patients with gynecologic cancers receiving carboplatin-based chemotherapy regimens who had participated in one of four institutional serotonin-receptor antagonist antiemetic trials, which had specifically evaluated the benefits of such therapy during only the first treatment course. Medical records were reviewed to examine the development of emesis during subsequent chemotherapy treatment cycles.. The 91 patients included in this analysis received a median of 6 courses (range 1-18) of carboplatin (initial AUC dose 4, 5, and 6 in 29, 29, and 32 patients, respectively). All received ondansetron or granisetron plus dexamethasone with every treatment course. Complete control of emesis (no acute or delayed nausea or vomiting) was experienced by 56 (62%) patients during every cycle. Conversely, 20% of women noted one or more episodes of nausea without vomiting and 19% developed at least one incidence of vomiting. In no case was emesis considered to be severe (grade 3), and no patient required either discontinuation of carboplatin or a dose reduction due to the development of emesis.. In the large majority of patients, serotonin-receptor antagonist antiemetic therapy, administered in combination with dexamethasone, is highly effective over multiple courses in preventing significant carboplatin-induced nausea and vomiting.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Clinical Trials as Topic; Dexamethasone; Drug Administration Schedule; Female; Genital Neoplasms, Female; Granisetron; Humans; Middle Aged; Nausea; Ondansetron; Retrospective Studies; Serotonin Antagonists; Taxoids; Vomiting