scholarly journals Clinical Prevalence of Chemotherapy-induced Peripheral Neuropathy in Onco-hematological Patients

2021 ◽  
Author(s):  
Katia Gleicielly Frigotto ◽  
Giovana Salviano Braga Garcia ◽  
Vitor Ribeiro Gomes de Almeida Valviesse ◽  
Karina Lebeis Pires
Keyword(s):  
Peripheral Neuropathy ◽  
Data Collection ◽  
Cancer Treatment ◽  
Dose Reduction ◽  
Side Effect ◽  
Douleur Neuropathique ◽  
Cancer Treatments ◽  
Hematological Patients ◽  
Study Support ◽  
Grade 3

Abstract Background Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a side effect common to many drugs in cancer treatment. CIPN symptoms are mainly sensory, as paresthesia and pain, especially in body extremities. It can affect the patient's life, requiring a dose reduction or interruption of therapy, which can impact patient's survival. Method Twenty-one hematology outpatients who were treated by neurotoxic potential drugs were selected. The Douleur neuropathique 4 questionnaire was applied, a patient form was made for data collection, and the data obtained was analyzed. Results The prevalence of CIPN was 47,62%. Five patients (23,81%) did not had signs of neurotoxicity, four (19,05%) patients were classified as Grade 1, seven (33,33% ) as Grade 2, and four (19,05%) as Grade 3, and one (4,76%) patient as Grade 4. Patients who had symptoms of CIPN had already received an average of 55,42% of the scheduled treatment. Three patients (14,29%) had to reduce the dose or change the drugs, and one patient (4,76%) had to discontinue it. Conclusions This study support the hypothesis that CIPN is an important side effect in cancer treatments. Being a cause of reducing the dose or temporarily suspending it, which can affect the success of the treatment and patient’s survival.

Velcade, Vorinostat and Dexamethasone (V2 D) in Relapsed Myeloma: Results of the Phase 2 Muk Four Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1852-1852
Author(s):  
Matthew W Jenner ◽  
Avie-Lee Tillotson ◽  
Sarah R Brown ◽  
Louise M Flanagan ◽  
Debbie Sherratt ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Disease Progression ◽  
Board Of Directors ◽  
Dose Reduction ◽  
Response Rate ◽  
Prior Treatment ◽  
Phase 2 ◽  
Advisory Committees ◽  
Grade 3 ◽  
Relapsed Myeloma

Abstract Introduction: Bortezomib (Velcade) and dexamethasone is a standard combination for relapsed myeloma. Both in vitro data and initial clinical trials signalled the efficacy of the combination of intravenous bortezomib and the oral histone deacetylase inhibitor vorinostat. Although the randomised phase 3 VANTAGE 088 trial identified an improvement in progression free survival with the combination of bortezomib and vorinostat compared to bortezomib monotherapy in relapsed myeloma, 50% of patients in the vorinostat group had at least one dose reduction compared with 25% in the placebo group, with potential impact on clinical outcomes. Subcutaneous bortezomib has now become the standard route of administration because of lower rates of peripheral neuropathy. MUK four is a single arm phase 2 multi-centre UK trial to evaluate the toxicity profile and efficacy of an alternative dosing schedule of vorinostat in combination with subcutaneous bortezomib and oral dexamethasone. We report the final analysis of toxicity and response data. Methods: Patients with relapsed myeloma treated with 1-3 prior lines of therapy received up to 8 cycles of V2 D (bortezomib 1.3 mg/m2 subcutaneously days 1, 4, 8 and 11, vorinostat 400 mg orally days 1-4, 8-11 and 15-18 and dexamethasone 20 mg orally days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21 day cycle). Following completion of a minimum of 3 cycles of V2 D, participants received maintenance vorinostat (400 mg days 1-4 and 15-18 of a 28 day cycle) until disease progression, intolerance or participant withdrawal. Responses were assessed using the modified IMWG response criteria and toxicities graded using CTCAE v4.0. Results: Between August 2013 and November 2014, 16 participants were recruited to MUK four. Median age was 69.5 years (range 50.0-78.0) and median lines of prior treatment was 1 (1-3). Prior treatment included thalidomide-based combinations in 13/16 (81.3%), bortezomib-based in 7/16 (43.8%) and lenalidomide-based in 2/16 (12.5%). 9/16 (56.3%) participants had received prior high dose melphalan ASCT. Median time from diagnosis was 38.6 months (9.3-120.4). At analysis in June 2015 8/16 (50%) participants continued on maintenance vorinostat. All 16 patients were evaluable for response within the first 8 cycles of V2 D. Overall response rate was 81.3% (13/16, 95% CI [55.4-96.0]) consisting of CR in 4/16 (25.0%), VGPR 2/16 (12.5%) and PR in 7/16 (43.8%). The remaining 3/16 (18.8%) achieved MR giving a clinical benefit response rate of 16/16 (100%). Participants received a median of 6 cycles of initial treatment with 6/16 (37.5%) receiving all 8 cycles. Treatment was discontinued in 4/8 (50%) because of disease progression, in 2/8 (25%) because of toxicity and in 2/8 (25%) for clinician discretion. Overall 12/16 (75%) participants experienced a dose reduction of either vorinostat or bortezomib or terminated treatment early as a result of toxicity. 11/16 (68.8%) reduced vorinostat and 10/16 (62.5%) reduced bortezomib. The most frequent grade 2 toxicities during the first 8 cycles were fatigue in 8/16 (50%), anaemia in 7/16 (43.8%), diarrhoea in 5/16 (31.3%), nausea in 4/16 (25.0%) and peripheral neuropathy in 4/16 (25.0%). The most frequent grade 3-4 toxicities encountered during the first 8 cycles were thrombocytopenia in 8/16 (50%), anaemia in 1/16 (6.3%), diarrhoea in 1/16 (6.3%) and fatigue in 1/16 (6.3%). During maintenance vorinostat only 1 participant experienced an adverse reaction above grade 2 (grade 3 neutropenia). Conclusion: Bortezomib, vorinostat and dexamethasone is a highly effective combination in relapsed myeloma with good response rates. Maintenance vorinostat is well tolerated. Although toxicity and dose reductions are observed with combination therapy, this study demonstrates that the combination of proteasome inhibitor, HDAC inhibitor and dexamethasone offers promise. Further data on PFS will be presented. Disclosures Jenner: Amgen: Honoraria; Takeda: Honoraria. Off Label Use: Vorinostat for treatment of myeloma. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Williams:Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Davies:Array-Biopharma: Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; Onyx-Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Nasal vestibulitis as an under-recognized and undertreated side effect of cancer treatment.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 219-219
Author(s):  
Elizabeth Jane Cathcart-Rake ◽  
DeAnne R. Smith ◽  
Charles L. Loprinzi
Keyword(s):  
Cancer Treatment ◽  
Targeted Therapies ◽  
Side Effect ◽  
Chart Review ◽  
Respiratory Illness ◽  
Concurrent Infection ◽  
Cancer Treatments ◽  
Treatment Regimens ◽  
Nasal Symptoms ◽  
Nasal Swabs

219 Background: Dryness, crusting, and bleeding of the nares due to inflammation, termed nasal vestibulitis (NV), is infrequently reported as a side effect of cancer treatments. However, one study described 115 patients who developed NV while undergoing targeted therapies; many were treated with bacitracin ointment (Ruiz et al Sup Care Cancer 2015). Methods: This study surveyed 94 patients regarding the presence of nasal symptoms during cancer treatments. Participants were consented for the study if they had undergone at least 6 weeks of cancer-directed therapy in the Mayo Clinic Chemotherapy Unit. They were asked about types of nasal symptoms, severity, and symptom treatments. A chart review was then conducted to determine documentation of symptoms, the presence of concurrent illnesses, and cancer treatment regimens. Results: Ninety-four patients completed questionnaires, with 41% reporting unpleasant nasal symptoms that they attributed to cancer treatments. Of the symptomatic patients, 46% had dryness, 33% had discomfort, 54% had bleeding, and 46% had scabbing. Average severity was 1.9 on a scale from 1 to 3 (1 = mild, 3 = severe). Symptoms were noted in patients undergoing a variety of cancer treatment regimens, with the highest frequency in patients undergoing a taxane-containing regimen (46%). 62% of patients with symptoms said they reported them to their provider, but only 41% of chart notes (for 16 patients) contained documentation of such, most frequently described as “allergies” or “epistaxis.” Only 10% of symptomatic patients had nasal swabs; all of which were obtained during respiratory illness or pre-op. 49% of patients with nasal symptoms reported treating their symptoms. Antihistamines (7 patients), nasal saline (6 patients), or nasal lubricants (i.e. Vaseline; 7 patients) were used; 2 patients applied bacitracin. 18% of symptomatic patients had providers who recommended treatments, including 2 patients who were thought to have concurrent infection and were treated with antibiotics. Conclusions: NV symptoms are prevalent among oncology patients, but infrequently recorded or treated by providers.

The Weekly Infusion of Bortezomib Reduces Peripheral Neuropathy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3887-3887 ◽  
Author(s):  
Francesca Gay ◽  
Sara Bringhen ◽  
Mariella Genuardi ◽  
Davide Rossi ◽  
Roberto Ria ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Research Funding ◽  
Low Dose ◽  
Discontinuation Rate ◽  
Weekly Administration ◽  
Advisory Committees ◽  
Weekly Infusion ◽  
Grade 3 ◽  
Weekly Group

Abstract Abstract 3887 Poster Board III-823 Background Peripheral neuropathy (PN) is a non-hematologic side effect frequently reported in elderly patients treated with bortezomib-melphalan-prednisone (VMP). To address this issue, both bortezomib-melphalan-prednisone-thalidomide (VMPT) and VMP dosing regimens were changed; and bortezomib schedule was modified from twice weekly to weekly administration. Aims To determine incidence and risk factors of bortezomib-associated PN in twice weekly or weekly bortezomib infusion schedules. Methods Patients (N=511) older than 65 years were randomly assigned to receive VMPT followed by maintenance with bortezomib and thalidomide or VMP. Initially, patients were treated with nine 6-week cycles of VMPT (induction: bortezomib 1.3 mg/m2 days 1,4,8,11,22,25,29,32 in cycles 1-4 and days 1,8,22,29 in cycles 5-9; melphalan 9 mg/m2 days 1-4; prednisone 60 mg/m2 days 1-4 and thalidomide 50 mg days 1-42; maintenance: bortezomib 1.3 mg/m2 every 15 days and thalidomide 50 mg/day as maintenance) or VMP (bortezomib, melphalan and prednisone at the same doses and schedules previously described without maintenance). In March 2007, the protocol was amended: both VMPT and VMP induction schedules were changed to nine 5-week cycles and bortezomib schedule was modified to weekly administration (1.3 mg/m2 days 1,8,15,22 in cycles 1-9). Baseline grade ≥ 2 PN was an exclusion criteria. Results 254 VMPT patients and 257 VMP patients were evaluated in intention-to-treat: 141 patients received twice weekly infusion of bortezomib and 370 once weekly. The overall incidence of PN was 37% in the VMPT patients and 27% in the VMP patients (p=0.01) while the grade ≥ 3 was quite similar (8% and 5%. p=0.19). When VMPT and VMP groups were combined, the incidence of PN was significantly higher in patients who received twice weekly infusion of bortezomib: the incidence of all grade PN was 45% in the twice weekly group and 27% in the once weekly group (p=0.0002), including a grade ≥ 3 PN incidence of 16% and 3% (p<0.0001), respectively (table 1). In multivariate analysis, the weekly infusion of bortezomib was the only predictive factor of lower incidence of PN (p<0.0001) whereas low-dose thalidomide did not affect PN rate (p=0.16). The weekly infusion of bortezomib significantly reduced discontinuation rate and bortezomib dose reduction (table 1). The weekly infusion of bortezomib slightly reduced the CR rate (p=0.07), but did not affect progression-free survival (p=0.31) and overall survival (p=0.44) (table 1). Conclusion The weekly infusion of bortezomib significantly decreased incidence of PN, discontinuation rate and dose-reduction rate without significant reduction of PFS. The addition of low-dose thalidomide to VMP did not increase the incidence of grade 3-4 PN. An update of these data and correlation between PN and clinical outcome will be presented at the meeting. Disclosures: Bringhen: Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Janssen-Cilag: Research Funding, consultancy and advisory committees; Celgene: Research Funding, consultancy and advisory committees; Pharmion: Research Funding, consultancy and advisory committees. Palumbo:Janssen-Cilag: Honoraria; Celgene: Honoraria.

The Combination of Cyclophosphamide, Velcade and Dexamethasone (CVD) Induces High Response Rates with Minimal Toxicity Compared to Velcade Alone (V) and Velcade Plus Dexamethasone (VD).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3537-3537 ◽  
Author(s):  
Faith E. Davies ◽  
Ping Wu ◽  
M. Srikanth ◽  
Matthew W. Jenner ◽  
Sharon Dines ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Synergistic Effects ◽  
Progression Free Survival ◽  
Response Rates ◽  
Complete Response ◽  
Chemotherapeutic Agents ◽  
Duration Of Treatment ◽  
Similar Frequency ◽  
Grade 3

Abstract Bortezomib (Velcade®), as the first-in-class proteasome inhibitor, has shown to be effective for the treatment of relapsed refractory myeloma. Preclinical and/or clinical studies showed improved activity by combining this agent with a number of conventional chemotherapeutic agents, suggesting synergistic effects. We conducted a retrospective study to assess the efficacy and toxicity profile with Velcade alone and in combination with dexamethasone or cyclophosphamide, and dexamethasone for patients with multiply relapsed myeloma. 11 patients were treated with Velcade alone, 20 with the combination of Velcade and dexamethasone (VD), and 11 with the regimen comprising Velcade, dexamethasone and cyclophosphamide (CVD). Velcade 1.3mg/m2 was given as a single bolus IV on days 1, 4, 8 and 11, dexamethasone 40mg po on the day of Velcade injection and the day thereafter, and cyclophosphamide 500 mg po days 1, 8, 15 of a 21 day cycle for a maximum of 9 cycles of treatment. No patient received prophylactic anticoagulation. Toxicity profiles and response were assessed every 3 weeks. There was no statistical difference of baseline characteristics (age, ISS, number of previous lines of treatment) among the three treatment groups (P>0.05). The overall response rates (CR+PR) within the three groups are 30% (V), 47% (VD), and 64% (CVD) respectively. The CR rate of CVD group is impressive at 27% compared to 5% with VD and 0% with V. The median duration of treatment of three groups (V vs VD vs CVD) are 115 days, 98 days and 116 days respectively (P>0.05). Thrombocytopenia and new/worsening peripheral neuropathy are the most common side effects in each group. Although thrombocytopenia and neutropenia occurred in the CVD group (36% and 27% respectively), it was at a similar frequency as in the groups of VD (50% and 15%) and V (64% and 45%). Grade 3 infection rates were also similar at 18%, 30% and 18% (V vs VD vs CVD). Peripheral neuropathy is the most troublesome side effect, and is the main reason for Velcade dose reduction and/or discontinuation in each group (27% V, 45% VD, 54% CVD). 27% of patients within CVD group required dose reduction of cyclophosphamide due to neutropenia. Median follow up is currently too limited to comment on whether the improved CR rate with CVD translates into an improved progression free survival. In conclusion CVD is a well tolerated regimen producing high overall and complete response rates, with no increase in toxicity compared to VD or V alone, and lacks the toxicity associated with Velcade- melphalan combinations.

Phase II trial of DJ-927, an oral tubulin depolymerization inhibitor, in the treatment of metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3591-3591 ◽  
Author(s):  
M. R. Moore ◽  
C. Jones ◽  
G. Harker ◽  
F. Lee ◽  
B. Ardalan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Grade 3

3591 Background: DJ-927, a novel oral tubulin depolymerization inhibitor, causes apoptosis and DNA cell division arrest. It is not a substrate for the MDR and has excellent activity in preclinical colorectal cancer models. Methods: We are conducting a two-stage, multi-center, phase II trial to assess the efficacy of DJ-927 administered initially as second-line therapy following failure of irinotecan or oxaliplatin based therapy (n= 39). DJ-927 is given as a single oral dose on day 1 of a 21-day cycle at a dose range of 27 - 35 mg/m2. Results: Thirty-nine patients were enrolled, including 14 with prior irinotecan based therapy and 25 who had received prior oxaliplatin therapy. The median age was 56 years (range: 30–87) and the median ECOG PS at baseline was 1 (range: 0–2). A total of 155 courses (range: 1–24) have been administered with a median of 2 courses. Nine patients required dose reduction due to toxicity. Thirty-seven patients were evaluable for efficacy. There were 2 CRs and 2 PRs (10.3%) reported that were confirmed as per RECIST criteria. Fourteen patients (35.9%) had SD, including 6 patients (15.4%) with SD >12 weeks. The most common Grade 3 or 4 AEs were neutropenia (48.7%), fatigue (10.3%), neuropathy (7.8%), and nausea (5.0%).Six patients experienced febrile neutropenia, all requiring hospitalization but tolerated treatment with subsequent dose reduction. There were 13 episodes (33.3%) of peripheral neuropathy reported; however, only 3 (7.8%) were grade 3 or 4. Six patients withdrew due to adverse events. Conclusions: The results of this study indicate activity of DJ-927 as second line therapy in patients with metastatic colorectal cancer. Severe toxicity was generally limited to reversible neutropenia and peripheral neuropathy. This novel oral agent is well tolerated and warrants further evaluation in combination with other active agents. [Table: see text]

scholarly journals Chemotherapy-induced peripheral neuropathy: a literature review

2011 ◽  
Vol 9 (4) ◽  
pp. 538-544 ◽  
Author(s):  
Lelia Gonçalves Rocha Martin ◽  
Maria Denise Pessoa Silva
Keyword(s):  
Peripheral Neuropathy ◽  
Literature Review ◽  
Activities Of Daily Living ◽  
Cancer Treatment ◽  
Side Effect ◽  
Daily Living ◽  
Common Side Effect ◽  
Common Condition ◽  
Significant Evidence

ABSTRACT Peripheral neuropathy is a common side effect in patients undergoing cancer treatment with chemotherapy. This condition can affect patients in several different ways, interfering in their activities of daily living and autonomy. The present study aimed to review the literature on chemotherapy-induced peripheral neuropathy and its treatment or other possible interventions. The findings reveal that chemotherapy-induced peripheral neuropathy is a common condition that affects patients undergoing treatment with some specific drugs. Besides, several different substances have been used to treat or control this condition, although no significant evidence could be found in these studies.

Frequency, Characteristics, and Reversibility of Peripheral Neuropathy During Treatment of Advanced Multiple Myeloma With Bortezomib

2006 ◽  
Vol 24 (19) ◽  
pp. 3113-3120 ◽  
Author(s):  
Paul G. Richardson ◽  
Hannah Briemberg ◽  
Sundar Jagannath ◽  
Patrick Y. Wen ◽  
Bart Barlogie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Gynecologic Oncology ◽  
Frequency Characteristics ◽  
Gynecologic Oncology Group ◽  
Neurologic Examination ◽  
Phase Ii Studies ◽  
Patient Reported ◽  
Grade 3

Purpose To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma. Patients and Methods Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m2 intravenous bolus on days 1, 4, 8, and 11, every 21 days, for up to eight cycles. Peripheral neuropathy was evaluated at baseline, during the study, and after the study by patient-reported symptoms using the Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire and neurologic examination. During the study, peripheral neuropathy was also evaluated by investigator assessment. A subset of patients underwent nerve conduction studies (n = 13). Results Before treatment, 194 (81%) of 239 patients had peripheral neuropathy by FACT/GOG-Ntx questionnaire, and 203 (83%) of 244 patients had peripheral neuropathy by neurologic examination. Treatment-emergent neuropathy was reported in 35% of patients, including 37% (84 of 228 patients) receiving bortezomib 1.3 mg/m2 and 21% (six of 28 patients) receiving bortezomib 1.0 mg/m2. Grade 1 or 2, 3, and 4 neuropathy occurred in 22%, 13%, and 0.4% of patients, respectively. The incidence of grade ≥ 3 neuropathy was higher among patients with baseline neuropathy by FACT/GOG-Ntx questionnaire compared with patients without baseline neuropathy (14% v 4%, respectively). In all 256 patients, neuropathy led to dose reduction in 12% and discontinuation in 5%. Of 35 patients with neuropathy ≥ grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%. Conclusion Bortezomib-associated peripheral neuropathy seemed reversible in the majority of patients after dose reduction or discontinuation. Although severe neuropathy was more frequent in the presence of baseline neuropathy, the overall occurrence was independent of baseline neuropathy or type of prior therapy.

Use of Immunoglobulin Infusions in the Management of Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5097-5097 ◽  
Author(s):  
Gerrard Teoh ◽  
Daryl Tan ◽  
William Hwang ◽  
Liang Piu Koh ◽  
Charles Chuah ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Intravenous Immunoglobulins ◽  
Modest Improvement ◽  
Asian Patients ◽  
Caucasian Patients ◽  
Grade 3 ◽  
And Function ◽  
Require Dose

Abstract Bortezomib (VELCADE) is a novel proteasome inhibitor that has shown tremendous clinical efficacy in Asian patients with multiple myeloma (MM). Prior studies have found that about a third (35%) of Caucasian patients develop bortezomib-induced peripheral neuropathy (PNY); and 12% and 5% of these patients require dose-reduction or discontinuation of bortezomib, respectively. Moreover, it has anecdotally been reported that a greater proportion of Asian patients receiving bortezomib develop PNY, and we are concerned that this unwanted effect of bortezomib would greatly limit the use of a drug that would otherwise be highly-effective for Asian MM patients. We therefore analyzed 20 Asian patients with MM who were treated with bortezomib, and found that up to 75% (15 out of 20) of patients developed bortezomib-induced PNY - sensory (75%) and/or motor (50%); confirming the observation that Asian patients are more prone to developing bortezomib-induced PNY. The majority of sensory PNY were mild. Grades 1 or 2 sensory PNY was seen in 45%, grade 3 in 15%, and grade 4 in another 15% of patients. Of these, 80% of patients reported painful neuropathies - 53% requiring dose reduction, and 27% requiring discontinuation of bortezomib. By contrast, motor PNY was more severe - 5% of patients reported grades 1 or 2, 15% with grade 3, and 30% with grade 4 motor PNY. In other words, if PNY develops in an Asian patient with MM, it is more likely to be a mild painful sensory PNY. However, if motor PNY occurs, it is more likely to be severe. For the treatment of PNY, all patients received gabapentin (600 mg to 1,400 mg per day), and 9 patients received L-carnitine (2 or 3 tablets a day). Gabapentin-treated patients reported only minimal effectiveness of this drug in relieving their symptoms, whereas no objective improvements were observed in all L-carnitine-treated patients. Similarly, amitriptyline was given to 3 patients with severe painful PNY and only a non-sustained modest improvement was reported in all these patients. In contrast, improvements of at least 1 grade in both symptoms and function were reported by all 9 patients who received intravenous immunoglobulins (IVIG). In the most significant of these, a patient who was bed-ridden because of grade 4 combined sensorimortor PNY, dramatically recovered (became pain-free, and improved to grade 2 motor weakness) within 2 days of completing IVIG 2.0 gm/kg divided over 4 days. In conclusion, Asian MM patients have indeed significantly higher rates of bortezomib-induced PNY, which unfortunately often leads to dose-reduction and/or discontinuation of bortezomib. Our data demonstrate that IVIG may be a useful agent for the management of these patients; and for facilitating the continued administration of bortezomib.

Fotemustine IN COMBINATION with BORTEZOMIB and DEXAMETHASONE: Encouraging PRELIMINARY RESULTS FROM A PHASE II STUDY On Relapsed REFRACTORY MYELOMA PATIENTS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3037-3037
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Federica Cocito ◽  
Cristiana Pascutto ◽  
Cesare Astori ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Phase Ii ◽  
Preliminary Data ◽  
Interim Analysis ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Median Number ◽  
Before And After ◽  
Grade 3

Abstract Abstract 3037 Fotemustine (Muphoran), a nitrosourea alkylating agent approved for use in the treatment of metastatic melanoma, has proven to be effective as single agent in relapsed/refractory multiple mieloma (MM). We report preliminary data of a phase II single centre study exploring the feasibility and the efficacy of the combination bortezomib (B) + fotemustine (Mu) + dexamethasone (D) (B-MuD) in relapsed/refractory MM patients. This study has been approved by local ethical committee; all patients (pts) signed written informed consent before the enrolment. MM pts relapsed or refractory after at least one therapy were eligible for the study. Pts who received prior bortezomib-containing regimen were included only if not considered bortezomib-refractory. Fotemustine at the escalating doses of 80 and 100 mg/m2 i.v. on day 1 was associated to Bortezomib 1,3 mg/m2 i.v. on days 1,4,8,11 + Dexamethasone 20 mg orally on days 1–2, 4–5, 8–9, 11–12 of 21-day cycle for a total of 6 cycles. Protocol was amended after the enrolment of the first five pts due to a considerable toxicity. We observed 3 grade 3–4 peripheral neuropathy, 1 grade 3 pneumonia, 4 grade 4 thrombocytopenia and two pts dropped-out (one for grade 3 pneumonia at 2° cycle, and one for grade 4 peripheral neuropathy at 3° cycles). Thus the schedule was modified as following: Fotemustine at escalating doses of 80 and 100 mg/m2 i.v. on day 1, Bortezomib 1,3 mg/m2 i.v. once weekly on days 1, 8, 15, 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, 22 for six 35-day cycles. An interim analysis of feasibility and efficacy was planned after the inclusion of the first two cohort of 6 pts each, treated with escalating dose of Fotemustine according to the amended schedule. Up to now, 18 pts have been enrolled (5 pts before and 13 after the amendment): M/F 10/8, median age 69 years (44-82), median number of previous therapies 2 (1-5). Previous treatments included autologous transplant in 10 pts (59%), bortezomib in 8 pts (44%), oral melphalan in 7 pts (41%) and thalidomide in 12 (71%). After the inclusion of 12 pts the MTD for Fotemustine was established to be 100 mg/m2. No drop-outs were registered after the amendment. Preliminary data on response are available in 10 pts. Nine pts (90%) obtained at least a PR, 8 pts (80%) registered ≥VGPR (CR 10%). At time of this analysis 79 cycles were delivered: 14 before, 65 after the amendment. Eighty-nine AE of any grade were observed, 43 hematological and 46 non-hematological. Thrombocytopenia was the most common AE either before and after the amendment. Need for dose reduction was significantly lower after the amendment. In detail fotemustine was reduced in 14% of cycles before and never after the amendment (p=0.0001), bortezomib dose reduction were performed in 36% of cycles before and 15% after the amendment (p=0.08), dexamethasone dose reduction occurred in 64% of cycles before and 13% after the amendment (p=0.0001). In conclusion, this interim analysis shows that fotemustine in combination with bortezomib and dexamethasone is safe and gives encouraging results in relapsed/refractory myeloma patients with 80% of ≥VGPR. Updated results will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Clinical Characteristics and Predictive Factors of Peripheral Neurophaty in Multiple Myeloma Patients Treated with Bortezomib and/or Imids

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4056-4056
Author(s):  
Vincenzo Federico ◽  
Russo Eleonora ◽  
Andrea Truini ◽  
Anna Levi ◽  
Fabiana Gentilini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Median Time ◽  
Predictive Factors ◽  
Neurological Examination ◽  
Clinical Characteristics ◽  
Douleur Neuropathique ◽  
Significant Difference

Abstract Abstract 4056 Background: Peripheral neuropathy (PN) and neuropathic pain are common and severe dose-limiting side effects of Bortezomib and/or IMIDs used in the management of multiple myeloma patients, which often requires dose reduction or interruption of treatment. Aims: We performed a monocentric prospective study to investigate the incidence, clinical characteristics and predictive factors of peripheral neuropathy and neuropathic pain in multiple myeloma patients treated with Bortezomib and/or IMIDs. Methods: All patients underwent clinical examination and were studied for the standard nerve conduction using the sural nerve action potential (SAP) trend. Neurological evaluation was performed monthly before, during and after Bortezomib and/or IMIDs treatment. Neuropathic pain was evaluated using the Douleur Neuropathique 4 (DN4) questionnaire and the Total Neuropathy Score reduced version. Results: Between January 2007 and June 2011, 145 consecutive patients, treated with Bortezomib and/or IMIDs, were prospectively studied. The clinical characteristics were: median age 60 years (range 32–78); 68 men and 77 women; 80 and 65 patients were, respectively, in Durie and Salmon stages I-II and III. Fifty-eight patients (40%) were treated with Bortezomib, 20 (14%) with Thalidomide, 37 (26%) with Lenalidomide and 30 (20%) with the Bortezomib-Thalidomide combination. After a median time of 3 months (range 1–22) from the start of our study, 100 patients (69%) developed a peripheral neuropathy during treatment; 78 (54%) patients had pain according to the DN4 questionnaire and 45 (31%) experienced neuropathic pain according to the Total Neuropathy Score. A significant difference (p<0.01) in terms of age and median time from diagnosis to the neurological examination was observed between patients with and without peripheral neuropathy. Patients with peripheral neuropathy were older and had a longer median time from diagnosis to the neurological examination: median age 59 vs 43 years (range 45–78 vs 32–62) and 45 vs 22 months (range 1–160 vs 1–36) from diagnosis. In addition, the different treatments were significantly associated with the development of peripheral neuropathy: the Bortezomib-Thalidomide combination and Bortezomib or Thalidomide alone were more frequently associated with peripheral neuropathy than Lenalidomide (p<0.05). No correlation between PN occurrence and cumulative dose of Bortezomib and IMIDs was observed. Among 30 patients (20%) treated with the Bortezomib-Thalidomide combination as first line of therapy, 22 (72%) experienced a peripheral neuropathy. In this group of patients, according to the SAP study, the neuropathy appeared after a median of 1.6 months of treatment and worsened after 3 months (Fig. 1). Sixteen patients continued Bortezomib-Thalidomide at the same dosage and 6 patients required a Bortezomib-Thalidomide dose reduction. An improvement of the neuropathy was observed after 4 months from the stop of treatment. Conclusions: Our data underline the clinical importance of peripheral neuropathy and pain in patients with multiple myeloma. Age, duration of disease and treatment are predictive factors of peripheral neuropathy development. The Douleur Neuropathique 4 (DN4) and Total Neuropathy Score questionnaires are useful tools to evaluate neuropathic pain. We also observed that a reduction of SAP occurs early in patients who developed a neuropathy that improves after the end of treatment. This finding could suggest the presence of biological factors predisposing to the development of neuropathy. Disclosures: Petrucci: Janssen, Celgene: Honoraria.

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