Background. Breast cancer is one of the most common female malignancies. Molecular diagnostic methods of tumor profiling allow us to analyze individual tumor characteristics, identify new prognostic and predictive markers. Aim. To increase the efficacy of systemic therapy for breast cancer and reduce inappropriate prescriptions using the data on individual molecular tumor characteristics; to develop a polygenic panel to ensure a tailored approach to systemic therapy for breast cancer. Materials and methods. We analyzed 84 tumor tissue samples from pre- and postmenopausal women with metastatic breast cancer who were treated and followed-up in 6 healthcare institutions. We assessed expression of genes involved in breast cancer. In a pilot study, we analyzed archived paraffin-embedded tumor specimens form 12 out of 1,216 patients with T1–2N0M0 breast cancer included into retrospective analysis. Gene expression was assessed using the nCounter technology based on direct digital detection of targets using fluorescent barcodes (nCounter Analysis System; NanoString Technologies, USA). Tumor tissue (biopsy and surgical specimens) was analyzed. The choice of genes was based on the literature data and experience in the development of other polygenic panels, as well as clinical significance of markers of prognostic scales. Gene mutations were confirmed by next generation sequencing and reverse transcription-polymerase chain reaction. Results. We analyzed the expression of 28 genes with a high predictive value that have been substantially studied (including ESR1, PGR, PIK3CA, BCAR4, BCAS2, CCND1, CCND2, CCND3, FOXA1, Erb2, EGFR, CDH3, FOXC1, KRT14, KRT5, CD274, CDK4, CDK6, P53, PTEN, BRCA1, BRCA2, CHEK2, CLDN3, CLDN7, AR, TOP2a, TUBBIII). We identified 29 cases of discrepancy (29 / 84; 34.5 %) in tumor subtype, including 11 cases of luminal A and B breast cancer, which might potentially affect the choice of the treatment regimen. In 18 cases, there were some principal discrepancies in the tumor subtype that implied totally different treatment regimens. The proposed polygenic signature allows accurate identification of the tumor subtype in patients with metastatic breast cancer and choice of an optimal treatment strategy. Conclusion. We have developed a 100-gene signature including molecular subtypes of breast cancer (luminal A, luminal B, basal, claudin-like) and treatment-oriented clusters. Molecular tumor profiling using this polygenic signature is an accurate method for determining tumor subtype in patients with breast cancer, which enables a tailored approach to therapy.

Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy. Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor. Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color‑coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer. Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+ / ISH±); and ≥15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression. Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2‑enriched molecular class and the response to anti‑HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.

Treatment of cancer often requires the use of adjuvant chemotherapy (ACT). In real clinical practice, numerous patients suffer from severe toxicity and reduced quality of life (QoL). Hence, there is a need to maintain QoL and to reduce therapy toxicity to comply with recommended chemotherapy (CT) regimens. The present study focused on the effects of the multi-component nutritional supplement Oncoxin (ONCX) on QoL and CT-induced toxicity in patients undergoing ACT. A total of 133 patients aged 50-70 years with gastric cancer IIB-IIIC or non-small cell lung cancer IIB-IIIA were enrolled in the present study: 84 received ONCX, and 49 were included in the control arm and received CT only. It was identified that after 2 weeks of treatment the patients receiving ONCX exhibited clinically meaningful improvement of QoL (measured by Edmonton Symptom Assessment System Questionnaire) compared with those in the control group (odds ratio, 2.07; 95% CI, 1.00-4.29). By the end of a 3 week-period, the albumin level was higher in patients of the ONCX group compared with those in the control group (mean, 38.1; 95% CI, 37.1-39.1 g/l; vs. mean, 35.5; 95% CI, 33.9-37.0; P=0.03; respectively). Furthermore, the use of ONCX substantively reduced the hepatic toxicity of ACT. The present prospective real clinical setting study revealed positive effects of ONCX on QoL and ACT toxicity. The present study was retrospectively registered under the study registration number NCT03550482 at ClinicalTrials.gov (June 8, 2018).

2528 Background: Plin has clinical anticancer activity in combination with Tax (Mohanlal ASCO-SITC 2017,18). Plin prevented Tax-induced neutropenia in a post-hoc analysis of a φ 2 trial (Blayney ASH 2016). Plin is being studied in the prevention of chemotherapy(chemo)-induced neutropenia (CIN) induced by Tax/ adriamycin/ cyclophosphamide in BC, by gemcitabine/ abraxane in PC, by carboplatin/ pemetrexed/ pembrolizumab in NSCLC , and irinotecan in CRC. We report final results of the φ 2 portion of a prospective φ 2/3 trial of Plin for CIN compared with Peg (NCT03102606; Study BPI-2358-105). The 105 study is designed to demonstrate non-inferiority (NI) of Plin vs Peg for duration of severe neutropenia (DSN) in φ 3. Methods: Patients (Pts; n = 55) with lung cancer (NSCLC) were randomized to Tax 75 mg/ m2 day (D)1, and either Peg 6 mg D2 or Plin 5, 10, or 20 mg/ m2 D1. Plin was dosed on the same day of (30 min after) chemo. Absolute Neutrophil Count (ANC) was collected D1,2,3,6,7,8,9,10,15 and 21. Primary endpoints were DSN and grade (Gr) 4 neutropenia to establish recommended phase 3 dose (RP3D). The NI margin for DSN is 0.65 D. Hypertension (HT) was evaluated by semi-continuous BP measurement on D1. Results: DSN for Peg was 0.51 D and for Plin 0.54 D. Gr 3 HT was transient and not different among all groups (p < 0.18). Bone Pain occurred in 33% of pts with Peg and 11% with 20 mg/ m2 Plin. Clinical trial information: NCT03102606. Conclusions: Plin 20 mg/ m2, given 30 min after chemo is well tolerated, has less bone pain, and has similar myeloprotective effect vs Peg. Its post chemo recovery curve is shallower, broader and later than Peg, with median ANC staying within normal range, suggesting a different MoA to prevent CIN. Plin 20 mg/m2 is the RP3D based upon its protection against Gr 4 neutropenia and safety profile. Dose Pts Median ANC (cell count x10E9/L)* Gr 4 CIN % D1 D6 D7 D8 D9 D10 D15 Peg 6 mg 14 9.43 4.65 5.82 12.1 15.7 16.7 11.4 14 Plin 20 mg/m2 14 7.39 4.25 3.57 2.69 2.25 2.41 3.97 14 Plin 10 mg/m2 13 7.93 4.13 1.91 1.76 1.94 2.30 4.69 23 Plin 5 mg/m2 14 7.63 3.57 1.73 1.33 1.42 1.95 3.21 21 * Normal range of ANC: 1.8 to 7.7 X 10^9 cells/L

Cetuximab in combination with an irinotecan‐containing regimen is a standard treatment in patients with KRAS wild‐type (KRAS WT), metastatic colorectal cancer (mCRC). We investigated the addition of the oral MET inhibitor tivantinib to cetuximab + irinotecan (CETIRI) based on preclinical evidence that activation of the MET pathway may confer resistance to anti‐EGFR therapy. Previously treated patients with KRAS WT advanced or mCRC were enrolled. The phase 1, open‐label 3 + 3, dose‐escalation study evaluated the safety and maximally tolerated dose of tivantinib plus CETIRI. The phase 2, randomized, double‐blinded, placebo‐controlled study of biweekly CETIRI plus tivantinib or placebo was restricted to patients who had received only one prior line of chemotherapy. The phase 2 primary endpoint was progression‐free survival (PFS). The recommended phase 2 dose was tivantinib (360 mg/m2 twice daily) with biweekly cetuximab (500 mg/m2) and irinotecan (180 mg/m2). Among 117 patients evaluable for phase 2 analysis, no statistically significant PFS difference was observed: 8.3 months on tivantinib vs. 7.3 months on placebo (HR, 0.85; 95% confidence interval, 0.55–1.33; P = 0.38). Subgroup analyses trended in favor of tivantinib in patients with MET‐High tumors by immunohistochemistry, PTEN‐Low tumors, or those pretreated with oxaliplatin, but subgroups were too small to draw conclusions. Neutropenia, diarrhea, nausea and rash were the most frequent severe adverse events in tivantinib‐treated patients. The combination of tivantinib and CETIRI was well tolerated but did not significantly improve PFS in previously treated KRAS WT mCRC. Tivantinib may be more active in specific subgroups.

8057 Background: BCD-021 demonstrated equivalence to Avastin in a comprehensive comparability exercise that included physicochemical, PK and PD studies, as well as phase I PK clinical study in patients with non-squamous NSCLC. Methods: 138 patients with advanced non-squamous NSCLC (stage IIIb/IV) were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-021 or Avastin at a dose of 15 mg/kg in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/ml×min) every 3 weeks up to 6 cycles of therapy or until progression or unbearable toxicity. Results: ORR (primary endpoint) in both groups had no statistically significant differences: 42.59 % (95% CI 30.33 – 55.83) in BCD-021 group and 39.29% (95% CI 27.58 – 52.27%) in Avastin group. The lower limit of 95% CI for ORR difference between the groups (-14.96%) did not exceed the non-inferiority margin, hence BCD-021 is non-inferior to Avastin. There were also no differences between the groups for all other efficacy parameters: CR (1.85% vs 1.79%), PR (40.74% vs 37.50%), stable disease (51.85% vs 51.79%) and progression rate (5.56% vs 8.93%) in BCD-021 and Avastin group, respectively. AEs profiles of BCD-021 and Avastin were equivalent. Rate of all observed AEs including severe AEs had no statistically significant difference between the groups. Most AEs were associated with chemotherapy : neutropenia (85.29% vs 78,7%), anemia (88.24% vs 84.85%), leukopenia (79.41% vs 75.76%), thrombocytopenia (69.12% vs 62.12%), hyperglycemia (61.76 vs 56.06), LDH increase (48.53 vs 37.88), ALP increase (35.29% vs 30.30), ALT increase (26.47% vs 28.79%), alopecia (30.88% vs 24,24%), etc. Reactions specific for bevacizumab included: arterial hypertension (26,47% vs 22,73%), weakness (17.65 vs 16.67), lung bleeding (5.88% vs 3.03%), proteinuria (2.94% vs 0%), GIT perforation (0% vs 1.52%) and VTE (0% vs 1.52%). Binding and neutralizing antibodies were transient and detected only in 1 patient in each group that indicated to low immunogenic potential of both drugs. Conclusions: BCD-021 demonstrated non-inferiority to Avastin in patients with NSCLC. Clinical trial information: NCT01763645.

e20735 Background: Empegfilgrastim is an innovator drug product of pegylated G-CSF indicated for prophylaxis of neutropenia in patients receiving myelosuppressive chemotherapy. Methods: Objective was to compare safety and efficacy of a single dose of empegfilgrastim and daily dosing of filgrastim in patients receiving docetaxel 75 mg/m2 + doxorubicin 50 mg/m2. 135 patients with breast cancer were randomly assigned at a ratio of 1:1:1 to receive either single s.c. injection of empegfilgrastim at doses of 6 mg or 7.5 mg, or daily s.c. injections of filgrastim at a dose of 5 mcg/kg (until ANC ≥ 10x109/L). Results: At the cycle 1 mean duration of grade 4 neutropenia (primary endpoint) was significantly shorter in both empegfilgrastim groups: 0,905, 0,791 and 1,725 days in 6 mg, 7.5 mg and filgrastim groups, correspondingly. Mean difference in duration of grade 4 neutropenia between filgrastim and 7.5 mg groups was -0,934 d (95% CI -1,504 to -0,364 d) (p < 0,05). During the next 3 cycles duration of grade 4 neutropenia was also significantly shorter in both empegfilgrastim groups: cycle 2 (0.452, 0.326 and 0.925 d), cycle 3 (0.244, 0.310 and 0.641 d), cycle 4 (0.195, 0.475 and 0.892 d) (p < 0.05). Bacterial infections were observed only in 4 patients from filgrastim group, all patients were treated with oral anti-infective drugs. Empegfilgrastim at both doses was as safe and well tolerated as daily filgrastim administration. Most AEs were associated with chemotherapy. Frequency of G-CSF-specific reactions as all other AEs was equivalent in all groups: myalgia (7.14%, 4.65% and 4.65%), arthralgia (14.29%, 6.98% and 6.98%), ossalgia (9.52%, 9.30% and 4.65%), local reactions (7.14%, 2.33% and 2.33%). Conclusions: The results of this study demonstrated therapeutic superiority of empegfilgrastim, especially at a dose of 7.5 mg, compared to filgrastim. Clinical trial information: NCT02104830. Empegfilgrastim 6 mg Empegfilgrastim 7.5 mg Filgrastim p value Febrile neutropenia cycle 1 1 (2.38%) 1 (2.33%) 1 (2.50%) p > 0.05 all cycles 1 (2.38%) 3 (6.98%) 1 (2.50%) p > 0.05 Severe neutropenia cycle 1 31 (73.81%) 29 (67.44%) 35 (87.50%) p > 0.05 all cycles 40 (95.24%) 34 (79.07%) 40 (100.00%) p < 0.05

e11576 Background: BCD-022 is a trastuzumab biosimilar candidate manufactured by CJSC BIOCAD, Russia. Full spectrum of physicochemical and preclinical studies showed equivalence of BCD-022 to innovator drug trastuzumab. Methods: 46 patients with HER2(+) mBC were enrolled in the study. Patients were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-022 or trastuzumab (a single loading dose 8 mg/kg a maintenance dose 6 mg/kg) with paclitaxel (175 mg/m2) every 3 weeks. The primary endpoint was AUC(0-504), the secondary endpoints included Cmax, T1/2 и Tmax. Trastuzumab serum concentrations were evaluated immediately before the first infusion and after 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h. Results: PK analysis demonstrated that 90% CI for ratio of geometric means of AUC(0-504) of trastuzumab after single BCD-022 and trastuzumab administration was 80.42–120.87%, for ratio of Cmax– 83.69–123.05%. These ranges were within pre-specified PK equivalence criteria of 80–125 % according to EMA recommendations (EMA/CHMP/BMWP/403543/2010). There were no statistically significant differences between the groups for all other PK secondary parameters. BCD-022 and trastuzumab were well tolerated without any significant differences in AEs frequency between the groups. The most common AEs included hematological toxicity (leukopenia, neutropenia and anemia), hyperglycemia, AST, ALT, ALP and LDH increase. Arterial hypertension, tachycardia, alopecia, myalgia and arthralgia were less frequent. The majority of AEs were of Grade 1-2 (CTCAE 4.03) and were associated with myelosuppressive chemotherapy. Conclusions: PK and safety characteristics of BCD-022 and trastuzumab after a single i.v. administration in patients with HER2(+) mBC are considered to be equivalent. These data allow continue BCD-022 study aimed to assess efficacy and safety in the same population. Clinical trial information: NCT01764022.

e13500 Background: BCD-021 is a bevacizumab biosimilar candidate manufactured by CJSC BIOCAD, Russia. Full spectrum of physicochemical and preclinical studies showed equivalence of BCD-021 to innovator drug Avastin. Methods: 28 patients with advanced non-squamous NSCLC (stage IIIb/IV) were enrolled in the study. Patients were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-021 or Avastin at a dose of 15 mg/kg in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/ml×min) every 3 weeks. The primary endpoint was AUC(0-504), the secondary endpoints included Cmax, T1/2 è Tmax. Bevacizumab serum concentrations were evaluated immediately before the first infusion and after 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h. Results: Pharmacokinetic (PK) analysis demonstrated that 90% CI for ratio of geometric means of AUC(0-504) of bevacizumab after single BCD-021 and Avastin administration was 80.01–118.28%. This range was within pre-specified PK equivalence criteria of 80–125 % according to EMA recommendations (EMA/CHMP/BMWP/403543/2010). There were no statistically significant differences between the groups for all other secondary PK parameters. BCD-021 and Avastin were well tolerated without any significant differences in AEs frequency between the groups. The most common AEs included leukopenia and neutropenia. All other AEs (hyperglycemia, AST, ALT, ALP and LDH increase, arterial hypertension, alopecia, arthralgia, peripheral neuropathy, weakness etc.) were less frequent. The majority of AEs were of Grade 1-2 (CTCAE 4.03) and were associated with myelosuppressive chemotherapy. Conclusions: PK and safety characteristics of BCD-021 and Avastin after a single i.v. administration in patients with NSCLC are considered to be equivalent. These data allow continue BCD-022 study aimed to assess efficacy and safety in the same population. Clinical trial information: NCT01763645.

e12012 Background: One of the most serious potential side effects of chemotherapy is neutropenia. Grade 3 and 4 neutropenia is especially problematic because of increased incidence of infections, hospitalization, antibiotic treatment, necessity to reduce therapy intensity. The intensity of adjuvant chemotherapy is the key to successful treatment. Dicarbamin is agent for the prevention of chemotherapy-induced neutropenia. Dicarbamin therapy decreases dystrophic changes in myeloid progenitor cells and decreases the relative number of cells with signs of apoptosis. We conducted an analysis of efficacy of dicarbamin in patients during docetaxel-based chemotherapy. Methods: Between May 2011 and July 2012, 87 patients with early breast cancer were treated with adjuvant DAC regimens (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 every 3 weeks). All patients were female. All patients were treated with these regimens without prophylactic growth factor support. 42 patients of control (group A) were not given any prophylaxis of neutropenia. 45 patients (group B) were given dicarbamin 100 mg/day on day 5 before chemotherapy administration. Treatment with dicarbamin continued for all treatment period. Neutropenia was evaluated with Common Toxicity Criteria, Version 3.0. Results: Median age was 47 (29 – 55). Grade 4 neutropenia was reported in 13 (30.9%) patients treated without dicarbamin (A) and in 8 (17.7%) patients treated with dicarbamin (B). Grade 4 neutropenia was observed in 39 cycles in group A and in 22 cycles in group B (p=0.016). The beneficial effect of dicarbamin was also demonstrated by a quick recovery of granulocytes levels than in controls. In 17 (37.7%) patients treated with dicarbamin granulocytes levels were normal all period of chemotherapy. The dose intensity of chemotherapy was more in group with dicarbamin prophilaxis. The toxicity of dicarbamin was not observed. Conclusions: Dicarbamin is an active agent for prophylaxis of neutropenia without specific toxicity. The intensity of the DAC-chemotherapy was more in group with dicarbamin prophilaxis.

3508 Background: Tivantinib (ARQ 197) selectively inhibits the MET receptor tyrosine kinase, which is implicated in tumor cell migration, invasion, and metastasis. Resistance to EGFR inhibitors has been associated with activation of alternative pathways including MET. Methods: Pts with advanced KRAS WT CRC that progressed on or after 1 prior line of chemotherapy and no previous treatment with an EGFR inhibitor were eligible. Pts were randomized 1:1 to receive cetuximab (500 mg/m2) and irinotecan (180 mg/m2) on days 1 and 15 every 28 days, plus oral tivantinib (360 mg twice daily [BID]) or placebo. The primary endpoint was progression-free survival (PFS); additional endpoints include safety, objective response rate, overall survival (OS) and exploratory biomarker analyses. Results: Between Jul 2010 and Feb 2012, 122 pts were randomized; 117 pts were eligible for analysis (60 tivantinib, 57 placebo). Mean age was 57 years (range, 27-79 years); ECOG PS 0/1 55%/45%; and 81% received prior oxaliplatin. Median PFS was 8.3 months in the tivantinib arm vs 7.3 months in the placebo arm (hazard ratio [HR] = 0.85; 95% CI, 0.55-1.33; P = 0.38). Objective response rate (95% CI) was 45% (33%-58%) in the tivantinib arm and 33% (23%-46%) in the placebo arm. Median OS has not yet been reached but is trending in favor of tivantinib vs placebo (HR = 0.67). Among pts with prior oxaliplatin therapy, median PFS was 8.4 months for tivantinib and 7.2 months for placebo (HR = 0.67; 95% CI, 0.44-1.00; P= 0.1). The most common grade 3/4 adverse events (≥ 10%) were neutropenia, diarrhea, and nausea. Correlation of clinical outcomes with additional factors including mutation status and immunohistochemical analysis of tumor MET expression will be presented. Conclusions: Outcomes in this trial trended towards improvement with tivantinib (360 mg BID) plus cetuximab and irinotecan, particularly in the subgroup who had previous oxaliplatin. Further studies are needed to identify the CRC population most likely to benefit from addition of tivantinib to standard therapy. Clinical trial information: NCT01075048.

An overview of ASCO, ESMO, EORTC, ASH recommendations for prevention and therapy the chemotherapy-induced neutropenia and anemia is presented. Update of EORTC guidelines (2010) to reduce the incidence of chemotherapy-induced febrile neutropenia and the studies on which the update was made are described. Patient assessment algorithm to determine primary prophylactic G-CSF usage is presented. The usage of erythropoietins and intravenous iron for treatment of chemotherapy-induced anemia is described in detail. Review can help haematologists and oncologists to select an optimal way to prevent hematological complications of chemotherapy.

The primary objective was to determine if a single dose of casopitant 90 mg added to ondansetron and dexamethasone would improve the control of chemotherapy-induced nausea and vomiting (CINV) over 0–120 h following initiation of oxaliplatin-based moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone.

PURPOSE This study evaluated the safety and efficacy of recombinant human intestinal trefoil factor (rhITF) administered as topical oral spray for prevention and treatment of chemotherapy-induced oral mucositis (OM). PATIENTS AND METHODS Ninety-nine patients with colorectal cancer who had moderate to severe OM (WHO grade >or= 2) in the first cycle of chemotherapy were randomly assigned to receive either placebo, rhITF 10 mg/mL (ie, low dose), or rhITF 80 mg/mL (ie, high dose) by oral spray (300 microL, eight times each day) for 14 consecutive days in the second chemotherapy cycle. Patients were assessed on days 1, 3, 5, 7, 10, 12, 14, and 21 (+/- 2 days for the last assessment) for safety and for OM incidence and severity. RESULTS Treatment of patients at high risk for developing OM with low- or high-dose rhITF significantly reduced the amount of incidence (75% to 81%; low-dose rhITF P < .001; high-dose rhITF P = .002). Frequencies of WHO grade >or= 2 OM in the placebo, low-dose rhITF, and high-dose rhITF groups were 48.5%, 9.1%, and 12.1%, respectively. Assessment of the area under the curve revealed statistically significant reductions in OM severity in the rhITF-treated groups versus placebo. Only a minority of patients (6.1%) reported treatment-emergent adverse events (TEAEs), all of which were mild to moderate in intensity and resolved without sequelae. The incidence of TEAEs was not significantly different among treatment groups. CONCLUSION rhITF oral spray formulation was safe and effective when used for the reduction of chemotherapy-associated OM in patients with colorectal cancer. Patients exhibited high compliance in dosing administration. Future clinical study is planned to develop this drug for use in OM management in patients with cancer.