Severe Non-hematological Adverse Events Research Articles

The Effecacy and Safety of Daratumumab Based Regimens in Relapsed/Refractory Multiple Myeloma: A Single-Center Real-World Data Analysis

To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of daratumumab on stem cell collection and engraftment. The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis. All 43 RRMM patients were treated with daratumumab-based combination regimens, including Dd, DVd, DRd, Dkd, DId, and Dara-DECP. With median follow-up time 10.1 (2.1-36.6) months, the best overall response rate (ORR) was 74.4% and a best complete response rate (CR) was 25.6%. 1-year overall survival rate (OS) was 84.5%. The most common severe hematologic adverse events (Grade>3) are 3/4 grade leukopenia（18.6%）, and the most common severe non-hematologic adverse events were infusion-related reactions (IRRs， 20.9%) and infections（7.0%）. Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS （P =0.004）. The use of daratumumab has no effect on stem cell collection, or engraftment. Daratumumab is safe and effective in RRMM.

CXCR4-Directed Imaging and Endoradiotherapy in Desmoplastic Small Round Cell Tumors.

Desmoplastic small round cell tumor (DSRCT) is a rare, radiosensitive, yet difficult-to-treat sarcoma subtype affecting predominantly male adolescents. Extensive intraperitoneal seeding is common and requires multimodal management. With no standard therapy established, the prognosis remains poor, and new treatment options are needed. We demonstrate the clinical potential of C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging and endoradiotherapy in DSRCT. Methods: Eight male patients underwent dual-tracer imaging with [18F]FDG and CXCR4-directed [68Ga]pentixafor PET/CT. A visual comparison of both tracers, along with uptake quantification in active DSRCT lesions, was performed. [68Ga]pentixafor uptake was correlated with immunohistochemical CXCR4 expression on tumor cells. Four patients with end-stage progressive disease underwent CXCR4-based endoradiotherapy. We report the safety, response by RECIST 1.1, and survival after endoradiotherapy. Results: Uptake of [68Ga]pentixafor in tumor lesions was demonstrated in all patients with DSRCT, providing diagnostic power comparable to [18F]FDG PET. Corresponding CXCR4 expression was confirmed by immunohistochemistry in all DSRCT biopsies. Finally, 4 patients were treated with CXCR4-directed [90Y]endoradiotherapy, 3 in a myeloablative dose range with subsequent autologous stem cell transplantation. All 3 required transfusions, and febrile neutropenia occurred in 2 patients (resulting in 1 death). Notably, severe nonhematologic adverse events were absent. We observed signs of response in all 3 patients, translating into disease stabilization in 2 patients for 143 and 176 d, respectively. In the third patient, postmortem autopsy confirmed a partial pathologic response. Conclusion: We validated CXCR4 as a diagnostic biomarker and a promising target for endoradiotherapy in DSRCT, demonstrated its feasibility, and provided the first evidence of its clinical efficacy.

Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum-based combination therapy for gastric cancer: a multicenter retrospective study

BackgroundIt is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy.MethodsWe evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0).ResultsA total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465–1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752–1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173).ConclusionThere was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.

The impact of single-hetero UGT1A1 on clinical outcomes of irinotecan monotherapy in gastric cancer after fluoropyrimidine, platinum, and taxanes: Multicenter retrospective study.

296 Background: Japanese gastric cancer treatment guidelines (5th edition) recommend irinotecan (IRI) after fluoropyrimidine, platinum and taxanes as a third line chemotherapy. We previously reported that patients with UGT1A1 single heterozygous (SH) had significantly high frequency of severe hematological adverse events (AEs) compared to patients with UGT1A1 wild type (WT) in IRI monotherapy for advanced gastric cancer (AGC). However, it remains unclear that UGT1A1 SH affect efficacy and safety of IRI after fluoropyrimidine, platinum and taxanes compared to WT as a salvage line. Methods: We retrospectively analyzed the clinical data of patients who received IRI monotherapy after fluoropyrimidine, platinum and taxanes in the multi-institutional retrospective study. From January 2010 to December 2017, 69 eligible patients were registered from 8 centers in Japan. Results: Forty one patients with UGT1A1 WT and 28 patients with UGT1A1 SH were included in this study. In WT/SH patients, performance status 0/1/≥2 was 12/25/4 and 5/17/6, treatment line 3rd/4th or later was 33/8 and 26/2, HER2 status positive/negative was 12/29 and 5/23, respectively. In WT/SH patients, rate of initial dose reduction was 22 and 28% (P = 0.363), median relative dose intensity (RDI) was 82% and 80% (P = 0.309). Of 88 patients who have measurable lesions, the overall response rate (ORR) was 5.7% and 4.2% (P = 1.000), disease control rate (DCR) was 54% and 38% (P = 0.289). Median progression free survival was 3.2 and 2.1 months (HR 0.607, P = 0.058) and median overall survival from initial day of IRI monotherapy was 10.0 and 7.0 months (HR 0.618 P = 0.086). In WT/SH patients, severe hematological AEs (≥G3) were observed more frequently in patients with UGT1A1 SH (WT: 43% and SH: 68%, P = 0.050), although frequency of severe non-hematological AEs (≥G3) were not significantly different in both groups (13% and 25%, P = 0.211). Conclusions: Compared to UGT1A1 WT, UGT1A1 SH status may be associated with poor efficacy and be a risk factor of higher frequency of severe hematological AEs.

166P - The comparison between UGT1A1 single heterozygous and wild type regarding the clinical outcomes of fixed dose irinotecan monotherapy for advanced gastric cancer: Multicenter retrospective study

BackgroundIrinotecan is a key drug for advanced gastric cancer (AGC). We previously reported that patients with UGT1A1 single heterozygous (SH) had significantly high frequency of severe hematological adverse events (AEs) compared to patients with UGT1A1 wild type (WT) in irinotecan monotherapy for AGC. However, the difference of initial dose and relative dose intensity (RDI) of irinotecan between UGT1A1 WT and SH might affect those results. Therefore, we compared between UGT1A1 SH and WT regarding the clinical outcomes of the fixed dose irinotecan monotherapy for AGC. MethodsWe retrospectively analyzed the clinical data of patients who received initial fixed dose irinotecan (150mg/m2, bi-weekly) in the multi-institutional retrospective study. 100 eligible patients were registered from 8 centers in Japan. ResultsThe number of patients with UGT1A1 WT/SH were 62 and 38, respectively. In WT/SH patients, performance status 0/1/≥2 was 20/40/2 and 11/23/4, treatment line 2nd/3rd or later was 27/35 and 18/20, HER2 positive/negative 17/45 and 8/30, respectively.In WT/SH patients, median PFS was 3.15 and 3.25 months (HR = 1.137, P = 0.543) and median OS was 10.4 and 7.3 months (HR = 0.734, P = 0.184). In WT/SH patients, dose reduction of Irinotecan was required in 30.6% and 50.0% (P = 0.053), delayed treatment due to AE was observed in 44.2% and 39.4% (P = 0.675), median treatment cycle was 6 and 4 (P = 0.278), and RDI was 0.86 vs 0.86(P = 0.864), respectively. Severe hematological AEs (≥G3) were 35.4% and 63.1%(P = 0.008) and severe non-hematological AEs (≥G3) were 6.5% and 15.8% (P = 0.173), respectively. Severe AEs in more than 5% patients were leukopenia (11.3% and 15.8%), neutropenia (14.5% and 31.6%), anemia (21.0% and 23.7%), and anorexia (1.6% and 10.5%). ConclusionsUGT1A1 SH patients who received initial fixed dose Irinotecan had high frequency of severe hematological AE compared to WT patients. However, there was no significant difference in efficacy of Irinotecan monotherapy in each group. Legal entity responsible for the studyYoshito Komatsu. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The impact of UGT1A1 single-hetero regarding the toxicity of fixed dose irinotecan therapy for advanced gastric cancer

Abstract Background Irinotecan is a key drug for advanced gastric cancer (AGC). We previously reported that patients with UGT1A1 single heterozygous (SH) had significantly high frequency of severe hematological adverse events (AEs) compared to patients with UGT1A1 wild type (WT) in irinotecan monotherapy for AGC. However, the difference of initial dose and relative dose intensity (RDI) of irinotecan between UGT1A1 WT and SH might affect those results. Therefore, we compared between UGT1A1 SH and WT regarding the clinical outcomes of the fixed dose irinotecan monotherapy for AGC. Methods We retrospectively analyzed the clinical data of patients who received initial fixed dose irinotecan (150mg/m2, bi-weekly) in the multi-institutional retrospective study. 106 eligible patients were registered from 8 centers in Japan. Result The number of patients with UGT1A1 WT/SH were 62 and 38, respectively. In WT/SH patients, performance status 0/1/≥2 was 20/40/2 and 11/23/4, treatment line 2nd/3rd or later was 27/35 and 18/20, HER2 positive/negative 17/45 and 8/30, respectively. In WT/SH patients, median PFS was 3.2 and 3.3 months (HR = 1.137, P = 0.543) and median OS was 10.4 and 7.3 months (HR = 0.734, P = 0.184). In WT/SH patients, median treatment cycle was 6 and 4 (P = 0.973), and RDI was 0.85 vs 0.84(P = 0.915), respectively. Hematological AEs were observed in 82.2% and 92.1% (P = 0.138), severe hematological AEs (≥G3) were 35.4% and 63.1%(P = 0.006). Non-hematological AEs were 88.7% and 86.8%(P = 0.507), severe non-hematological AEs (≥G3) were 6.6% and 15.8% (P = 0.122), respectively. Severe AEs in more than 5% patients were leukopenia (11.3% and 15.8%), neutropenia (14.5% and 31.6%), anemia (21.0% and 23.7%), and anorexia (1.6% and 10.5%). Conclusion UGT1A1 SH patients who received initial fixed dose Irinotecan had high frequency of severe hematological AE compared to WT patients. However, there was no significant difference in efficacy of Irinotecan monotherapy in each group.

1571P - Predicting chemotherapy toxicity in elderly patients with advanced non-small cell lung cancer: A prospective multicenter study of the National Hospital Organization in Japan

BackgroundPrevious studies have developed risk stratification schemas to assess chemotherapy toxicity. However, it is controversial which geriatric assessment variables should be used to assess the individual risk of severe toxicity from chemotherapy in elderly patients. MethodsPatients aged ≥70 years with advanced non-small cell lung cancer (NSCLC) treated at 24 National Hospital Organization institutions completed a pre-1st-line chemotherapy assessment, including the following: patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. Patients were followed through one cycle of chemotherapy to assess grade 3 (severe) to grade 5 (death) adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. We also analyzed clinical outcomes of all patients. ResultsIn total, 348 advanced NSCLC patients with a median age of 76 years (range, 70 to 95 years) joined this prospective study. In all patients, the best objective response rate and disease control rate were 35.6% and 81.0%, respectively. Severe adverse events ≥grade 3 occurred in 136 patients (39.1%). Functional status (performance status, daily life independence level, and Barthel index; p=0.0037, 0.0023, and 0.0214, respectively, between the ≥grade 3 cohort and the grade 0-2 cohort) and laboratory test results (anemia, albumin, and lactate dehydrogenase; p=0.0497, 0.0171, and 0.0060 respectively, between the ≥grade 3 cohort and the grade 0-2 cohort) affected the occurrence of severe non-hematologic adverse events. For hematologic adverse events, body mass index, Charlson comorbidity, daily life independence level, recognition status, treatment variables, and anemia were involved with the occurrence of severe adverse events (p=0.0488, 0.0333, 0.0358, 0.0276, < 0.0001, and 0.0271, respectively, between the ≥grade 3 cohort and the grade 0-2 cohort). ConclusionsGeriatric assessment variables and several laboratory test values independently predicted vulnerability to chemotherapy in elderly patients with advanced NSCLC. Clinical trial identificationUMIN000010384. Legal entity responsible for the studyThe National Hospital Organization in Japan. FundingThe National Hospital Organization in Japan. DisclosureAll authors have declared no conflicts of interest.

P-011 - The comparison between UGT1A1 single heterozygous and wild-type regarding the clinical outcomes of fixed-dose irinotecan monotherapy for advanced gastric cancer: a multicenter retrospective study

Abstract Background Irinotecan is a key drug for advanced gastric cancer (AGC). We previously reported that patients with UGT1A1 single heterozygous (SH) had significantly high frequency of severe hematological adverse events (AEs) compared to patients with UGT1A1 wild type (WT) in irinotecan monotherapy for AGC. However, the difference of initial dose and relative dose intensity (RDI) of irinotecan between UGT1A1 WT and SH might affect those results. Therefore, we compared between UGT1A1 SH and WT regarding the clinical outcomes of the fixed dose irinotecan monotherapy for AGC. Methods We retrospectively analyzed the clinical data of patients who received initial fixed dose irinotecan (150mg/m2, bi-weekly) in the multi-institutional retrospective study. 100 eligible patients were registered from 8 centers in Japan. Results The number of patients with UGT1A1 WT/SH were 62 and 38, respectively. In WT/SH patients, performance status 0/1/≥2 was 20/40/2 and 11/23/4, treatment line 2nd/3rd or later was 27/35 and 18/20, HER2 positive/negative 17/45 and 8/30, respectively.In WT/SH patients, median PFS was 3.15 and 3.25 months (HR = 1.137, P = 0.543) and median OS was 10.4 and 7.3 months (HR = 0.734, P = 0.184). In WT/SH patients, dose reduction of Irinotecan was required in 30.6% and 50.0% (P = 0.053), delayed treatment due to AE was observed in 44.2% and 39.4% (P = 0.675), median treatment cycle was 6 and 4 (P = 0.278), and RDI was 0.86 vs 0.86(P = 0.864), respectively. Severe hematological AEs (≥G3) were 35.4% and 63.1%(P = 0.008) and severe non-hematological AEs (≥G3) were 6.5% and 15.8% (P = 0.173), respectively. Severe AEs in more than 5% patients were leukopenia (11.3% and 15.8%), neutropenia (14.5% and 31.6%), anemia (21.0% and 23.7%), and anorexia (1.6% and 10.5%). Conclusions UGT1A1 SH patients who received initial fixed dose Irinotecan had high frequency of severe hematological AE compared to WT patients. However, there was no significant difference in efficacy of Irinotecan monotherapy in each group. Legal entity responsible for the study Yoshito Komatsu. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

S-1 in combination with docetaxel and oxaliplatin in patients with advanced gastro-esophageal adenocarcinoma: two parallel phase 1/2a studies

Background: Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended dose (RD), dose limiting toxicity (DLT) and safety of docetaxel in combination with oxaliplatin (O) and S-1 (DOS) in Caucasian patients with aGEA.Methods: We present final results of two parallel phase 1/2a studies (3 + 3 design). Escalating doses of docetaxel and S-1 with fixed dose O were given for 18 weeks every second week (DOS2w) or every third week (DOS3w) followed by S-1 maintenance therapy.Results: Thirty-four patients (18 in DOS2w and 16 in DOS3w) were enrolled between October 2013 and June 2015. Median age was 65 years (range 49–78). DLT was most often febrile neutropenia. Most common severe non-hematological adverse events were diarrhea (9%) and fatigue (6%). The RD of DOS3w was: docetaxel 50 mg/m2, O 100 mg/m2 and S-1 25 mg/m2 twice daily and of DOS2w was: docetaxel 40 mg/m2, O 70 mg/m2 and S-1 35 mg/m2 twice daily. Overall, response rate was 56%; median progression-free survival was 9.1 months; and median overall survival was 13.2 months in 34 patients.Conclusions: At the RD, DOS2w and DOS3w showed an acceptable safety profile in patients with aGEA.Clinical trials ID: NCT-01928524 and EudraCT 2012-005187-10

O2-12-3 - Retreatment with bendamustine in patients with relapsed/refractory indolent B-cell lymphoma and mantle cell lymphoma

Background: Bendamustine (Ben) and combinations of Ben/rituximab(R) therapies have shown high efficacy in relapsed/refractory indolent B-cell non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL). There are few data including efficacy and toxicity about retreatment with Ben after relapse. Patients and methods: Ten pts (4 follicular lymphoma, 3 other low grade B-cell lymphoma, 3 MCL) who had been previously successfully treated with the first Ben and maintained its efficacy for over 6 months were retreated with Ben between December 2010 and November 2015. The median age was 72 years (56-77) and the sex was 4 males and 6 females. Pts received Ben at 90-120mg/m2 on day 1 and 2 in a 21-28 days cycle for up to 6 cycles. R (375mg/m2) was added on day 1 in 9 pts. Prophylactic acyclovir and trimethoprim-sulfamethoxazole (ST) were used. Granulocyte colony-stimulating factor (G-CSF) was administered in case of severe neutropenia. The median observation duration was 46 months (18-60) from the first treatment and 18 months (2-35) from retreatment. Results: The number of previous regimens was 2 (1-5). An overall response rate was 90% (60% complete response rate (CR) and 30% partial response) by 5 cycles (2-6) of Ben. Those 9 pts previously obtained CR by the first Ben. Another 1 pt who had previously obtained stable disease (SD) by the first Ben got CR by retreatment of Ben. Response duration was 19 months (2-28). 1 Pt obtained CR after 2nd retreatment. Grade 3 or 4 reversible hematologic toxicities were observed. Severe non-hematologic adverse events were not observed. Although cytomegalovirus (CMV) antigenemia was observed in 3 pts, the treatment for CMV was not required. Conclusion: Our data suggests high activity and good tolerance of Ben retreatment (with R) in pts with relapsed/refractory lymphoma despite previous Ben treatment. In this point of view, prospective studies should be considered to establish efficacy and safety of Ben retreatment.

Cross-Intolerance With Dasatinib Among Imatinib-Intolerant Patients With Chronic Phase Chronic Myeloid Leukemia.

BCR-ABL inhibitors have improved the prognosis of patients with chronic myeloid leukemia (CML). However, imatinib, the first approved BCR-ABL inhibitor, must be discontinued in many patients because of resistance or intolerance. The present retrospective, pooled analysis of phase II and III data explored the extent of cross-intolerance between imatinib and dasatinib, a second-generation BCR-ABL inhibitor, in 271 CML imatinib-intolerant patients. Overall, 47 patients (17%) had cross-intolerance to dasatinib, determined by recurrence of grade 3 or 4 adverse events (AEs). Of the 228 patients who discontinued imatinib because of nonhematologic intolerance, 10 (4%) experienced the same severe nonhematologic AEs with dasatinib, with 4 of these patients (2%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients who discontinued imatinib because of hematologic intolerance, 37 (86%) experienced a recurrence of grade 3 or 4 hematologic AEs with dasatinib, with 8 patients (19%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients taking dasatinib at the optimized dose of 100 mg/d, 1 (2%) discontinued therapy because of recurrence of nonhematologic AEs and 3 (7%) because of recurrence of hematologic AEs. With a median treatment duration of 22 months, the estimated rates of progression-free survival and overall survival at 2 years were greater for patients with nonhematologic versus hematologic intolerance to imatinib who switched to dasatinib (progression-free survival, 94% vs. 68%, respectively; overall survival, 98% vs. 88%, respectively). Dasatinib could be an appropriate treatment option for imatinib-intolerant patients with CML, with cross-intolerance resulting in discontinuation in a few patients.

P1-22-1 - Retreatment with Bendamustine in Patients with Relapsed/Refractory Indolent B-Cell Lymphoma and Mantle Cell Lymphoma

Background: Bendamustine (Ben) and combinations of Ben/rituximab(R) therapies have shown high efficacy in relapsed/refractory indolent B-cell non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL). No data exist about Ben retreatment after relapse, concerning efficacy and toxicity in these patients (pts) population.Patients and methods: Six pts (3 with follicular lymphoma, 1 lymphoplasmacytic lymphoma, 2 MCL) who had previously successfully been treated with first Ben and maintained its efficacy for over 6 months were retreated with Ben between December 2010 and November 2013. The median age was 72 years (61-75) and the ratio of gender was 2 males and 4 females. Pts received Ben at 90-120mg/m2 on day 1 and 2 in a 21-28 days cycle for up to 6 cycles. R (375mg/m2) was added on day 1 in 5 pts. Prophylactic acyclovir and trimethoprim-sulfamethoxazole (ST) were used. Granulocyte colony-stimulating factor (G-CSF) was administered in case of severe neutropenia. The observation duration was 30 months (18-33) from the first treatment and 6 months (2-11) from retreatment.Results: The number of previous regimens was 2 (1-5). An overall response rate of 83.3% (5 in 6 pts) (33.3% complete response rate (CR) and 50% partial response) was observed by 5 cycles (2-6) of Ben. Those 5 patients previously obtained CR by the first Ben. Another 1 pt who had previously obtained stable disease (SD) by the first Ben again got SD by retreatment of Ben. Response duration was 6 months (4-10). Grade 3 or 4 reversible hematologic toxicities were observed. Severe non-hematologic adverse events were not observed. Although cytomegalovirus (CMV) antigenemia was observed in 3 pts, the treatment of CMV was not required.Conclusion: Our data suggest high activity and good tolerance of Ben retreatment (and R) in pts with relapsed/refractory lymphoma despite previous Ben treatment. In view of this, prospective studies should be considered to establish efficacy and safety of Ben retreatment.

Retrospective analysis of 27 consecutive patients treated with docetaxel/nedaplatin combination therapy as a second-line regimen for advanced esophageal cancer

The aim of this study was to evaluate the efficacy and safety of combination therapy with docetaxel and nedaplatin in advanced esophageal cancer as a second-line regimen in an outpatient setting. Twenty-seven consecutive patients with advanced esophageal cancer who received docetaxel/nedaplatin combination therapy as a second-line regimen were retrospectively evaluated. The combination therapy consisted of intravenous administration of docetaxel 30 mg/m(2) and nedaplatin 40 mg/m(2) every 2 weeks. The patients received a median of 7.4 cycles of treatment (range, 2-25 cycles ). No complete response was observed, and 3 of the 27 patients (11%) achieved partial responses. The disease control rate (partial response + stable disease) was 52%. The median survival time (MST) was 11.4 months. Severe hematological adverse events (grade 3-4) were: neutropenia (n = 10; 37%) and anemia (n = 5; 19%); there was neither febrile neutropenia nor grade 3-4 thrombocytopenia. Furthermore, no severe nonhematological adverse events or treatment-related deaths were observed. Combination therapy of docetaxel with nedaplatin was safe and well tolerated; however, the development of more effective therapy is warranted to improve the prognosis of esophageal cancer.

A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome

AbstractThis multicenter phase 2 study evaluated the use of tipifarnib (R115777) in patients with poor-risk myelodysplastic syndrome (MDS; French-American-British classification). Patients (n = 82) received tipifarnib 300 mg orally twice daily for the first 21 days of each 28-day cycle. Twenty-six patients (32%) responded to tipifarnib: 12 (15%) complete responses (CRs) and 14 (17%) hematologic improvements; 37 patients (45%) had stable disease (modified International Working Group criteria, 2006). Among the 12 CRs, the median response duration was 11.5 months (range, 2.0-21.9 months), the median time to progression was 12.4 months (range, 3.9-23.8 months), and 7 were still alive at time of analysis (all > 3 years). Median overall survival was 11.7 months (95% CI, 9.4-15.0). Grade 3-4 neutropenia (18%) and thrombocytopenia (32%) were the most common treatment-related adverse events; severe nonhematologic adverse events were rarely reported. In this study, durable responses and acceptable side effects were observed. Tipifarnib is an active agent for the treatment of patients with intermediate- to high-risk MDS.