Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial.

BACKGROUND: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. METHODS: Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). RESULTS: A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49-0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. CONCLUSIONS: Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

Romiplostim in primary immune thrombocytopenia that is persistent or chronic: phase III multicenter, randomized, placebo-controlled clinical trial in China.

Background: Multiple trials have confirmed that romiplostim could increase platelet count in individuals with primary immune thrombocytopenia (ITP), but no related study has assessed Chinese patients. Objectives: To assess the effectiveness of romiplostim as a second-line treatment of persistent or chronic ITP in Chinese adults. Methods: This phase III multicenter, randomized, placebo-controlled, double-blind, then open-label clinical trial (NCT02868099, CTR20150395) was conducted at 28 investigational sites in China. The patients were randomly assigned (3:1) to romiplostim (starting and maximum doses of 1 and 10 µg/kg, respectively) or placebo for 9 weeks (double-blind period), followed by the open-label period (both groups administered romiplostim) to week 22. The primary endpoint was the time (in weeks) during which platelet counts were ≥50 × 109/L in the double-blind period. Results: In this study, 202 patients (romiplostim, n = 151; placebo, n = 51) started the treatment. The median (range) numbers of weeks with platelet response after 6 weeks of treatment were 2 (0-6) and 0 (0-2) in patients administered romiplostim and placebo, respectively (P < .001). During the double-blind period, the proportions of patients with treatment-emergent adverse events were comparable between the romiplostim and placebo groups (82.8% vs 82.4%). The treatment-emergent adverse event with ≥10% difference in incidence between these 2 groups was injection site bleeding (1.3% vs 11.8%). Conclusion: Romiplostim significantly increased the time with maintained platelet response in patients with persistent or chronic ITP in comparison with placebo. No new safety signal was observed. Trial registration: ClinicalTrials.gov, NCT02868099. www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml, CTR20150395.

Safety and efficacy of hetrombopag in patients with chronic immune thrombocytopenia: a single-arm, open-label, multi-center phase 1 study.

Background: Thrombopoietin receptor agonists (TPO-RAs) are promising therapeutic strategy for patients with immune thrombocytopenia (ITP). We conducted this phase 1 trial (NCT02614846) to evaluate the preliminary efficacy and safety of hetrombopag (a TPO-RA) in patients with ITP. Methods: Patients with ITP who had an insufficient response or had progressed on at least one standard treatment for ITP were given hetrombopag orally at an initial dose of 5 mg once daily for up to 6 weeks. The primary endpoint was the proportion of patients who achieved platelet counts of ≥50×109/L at week 6. Results: A total of 37 eligible patients received hetrombopag treatment. This study met its primary endpoint, 22 (59.5%, 95% CI: 42.1-75.3) patients responded to hetrombopag, achieving platelet counts ≥50×109/L at week 6. Of the 29 (78.4%, 95% CI: 61.8-90.2%) patients who responded at least once during the study, the median time from treatment initiation to first response was 2.1 weeks (95% CI: 1.3-4.1 weeks). The median accumulative response duration was 3.1 weeks [interquartile range (IQR), 2.1-4.1 weeks]. The incidence of bleeding was reduced with hetrombopag treatment compared to the baseline. Adverse events (AEs) occurred in 32 (86.5%) patients and treatment-related AEs occurred in 13 (35.1%) patients. Two (5.4%) serious AEs were reported, but neither were treatment related. The dose was modified in one (2.7%) patient due to an AE. There were no incidences of treatment discontinuation/interruption or death. Conclusions: Hetrombopag showed preliminary activity in elevating platelet counts and reducing bleeding in patients with chronic ITP who had received at least one standard therapy. It was well-tolerated.

Dose tapering to withdrawal stage and long-term efficacy and safety of hetrombopag for the treatment of immune thrombocytopenia: Results from an open-label extension study.

BACKGROUND: The efficacy of hetrombopag in Chinese patients with immune thrombocytopenia (ITP) has been demonstrated in a randomized, double-blind, placebo-controlled, multicenter, phase III trial (NCT03222843). OBJECTIVE: This study aimed to report comprehensive data on a ≤6-week dose tapering to withdrawal (Stage 3) and an additional 24-week long-term extension period (Stage 4) in this phase III trial. PATIENTS/METHODS: Patients who fulfilled the screening criteria were eligible to enter Stage 3 or 4. During Stage 3, hetrombopag was gradually tapered to withdrawal. During Stage 4, hetrombopag treatment was initiated at 2.5, 3.75, 5, or 7.5 mg once daily. The efficacy endpoints during Stage 3 or 4 and the safety profile during the entire treatment period were reported. RESULTS: Among 194 patients who entered Stage 3, 171 (88.1%) relapsed. The median time to the first relapse since the start of Stage 3 was 15.0 days (95% CI, 14.0-16.0). In Stage 4, 144 (42.5%) patients responded at ≥75% of their assessments and 254 (74.9%) patients achieved platelet count ≥30 × 109 /L at least once, which was at least twice their baseline platelet count in the hetrombopag group (n = 339). The most common adverse events were upper respiratory tract infection (53.1%), thrombocytopenia (27.1%), and urinary tract infection (21.2%) in the hetrombopag group. CONCLUSION: The majority of patients who experienced dose tapering to withdrawal experienced a relapse. Long-term treatment with hetrombopag was effective in increasing and maintaining platelet count within the desired range in Chinese adults with ITP. Hetrombopag was well tolerated.

A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia.

BACKGROUND: Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS: Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 109/L) after 8 weeks of treatment. RESULTS: The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS: In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.

Ibrutinib in CLL/SLL: From bench to bedside (Review).

B-cell receptor (BCR) signaling is important for the development and maturation of normal B-cells and plays a key role in B-cell malignancies. Bruton's tyrosine kinase (BTK), a crucial terminal kinase enzyme in BCR signaling, has emerged as an attractive target and has been successfully applied in the treatment of hematological malignancies. Ibrutinib, a BTK inhibitor, has demonstrated marked efficacy and tolerability in treatment-naïve, relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). Ibrutinib has been approved by the Food and Drug Administration (FDA) for the treatment of CLL/SLL, MCL, marginal zone lymphoma and Waldenström macroglobulinemia and by the China FDA for the treatment of CLL/SLL and MCL. Clinical trials of ibrutinib, as a single agent or combined with chemoimmunotherapy and other promising novel agents in the treatment of B-cell malignancy therapy, such as diffuse large B-cell lymphoma, follicular lymphoma, multiple myeloma, primary and secondary CNS lymphoma and acute lymphoblastic leukemia, T-cell lymphoma and myelodysplastic syndrome, are ongoing (https://clinicaltrials.gov/). The aim of the present review was mainly to cover the clinical developments regarding the use of ibrutinib in the treatment of CLL/SLL, as well as its safety and toxicity profile.

Metformin and cancer: An existing drug for cancer prevention and therapy.

Metformin is a standard clinical drug used to treat type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome. Recently, epidemiological studies and meta-analyses have revealed that patients with T2DM have a lower incidence of tumor development than healthy controls and that patients diagnosed with cancer have a lower risk of mortality when treated with metformin, demonstrating an association between metformin and tumorigenesis. In vivo and in vitro studies have revealed that metformin has a direct antitumor effect, which may depress tumor proliferation and induce the apoptosis, autophagy and cell cycle arrest of tumor cells. The mechanism underpinning the antitumor effect of metformin has not been well established. Studies have demonstrated that reducing insulin and insulin-like growth factor levels in the peripheral blood circulation may lead to the inhibition of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin (mTOR) signaling or activation of AMP-activated protein kinase, which inhibits mTOR signaling, a process that may be associated with the antitumor effect of metformin. The present review primarily focuses on the recent progress in understanding the function of metformin in tumor development.

RNA interfering of CXCR4 inhibits the adhesion, invasion, and tumorigenicity of acute monocytic leukemic cells in vivo.

To investigate the effect of CXCR4 gene expressing on the proliferation, adhesion, and invasion of human monocytic leukemic cell line SHI-1 and its tumorigenic capacity in nude mouse. The SHI-1 cells were firstly infected with the rescued recombinant lentivirus to establish SHI-1/CXCR4i cell line. The expression of CXCR4, MMP-2 and MMP-9 in the SHI-1/CXCR4i cell was determined by real time quantitative PCR and flow cytometry. MTT assay was performed to detect the SHI-1/CXCR4i cell proliferative rate. The co-culture system of the leukemia cells with bone marrow stromal cells was utilized to detect the adhesive and migratory ability of SHI-1/CXCR4i cell. The nude mouse was subcutaneously inoculated with both cell lines, and then used to evaluate the growth ability of leukemia cells without CXCR4 expressing. The expression of CXCR4 mRNA in established SHI-1/CXCR4i cells decreased by 76% comparing with that in SHI-1/NC cells, which were infected with negative control virus. The proliferative rate of the SHI-1/CXCR4i cells in vitro did not show obvious difference with the SHI-1/NC cells, however, the adhesive and trans-Matrigel invasive ability were significantly decreased. Notably, the neoplasm was not observed in mice subcutaneously inoculated with SHI-1/CXCR4i cells, but presented in the SHI-1/WT and SHI-1/NC cells-inoculated mice in neoplastic volume of both groups. The present data showed that the CXCR4 silencing reduced the adhesive and migratory ability of SHI-1 cells in vitro, and suppressed the formation of subcutaneous neoplasm in vivo, demonstrating that the CXCR4 can be served as a novel target for leukemia gene therapy.

Chronic Myelocytic Leukemia (CML) Patient-Derived Dendritic Cells Transfected with Autologous Total RNA Induces CML-Specific Cytotoxicity.

The oncogenic bcr/abl1 fusion gene is a chronic myelogenous leukemia (CML)-specific antigen which is absent in normal tissues. This makes bcr/abl1 a perfect target for developing CML vaccines that elicit specific immune responses against minimal residual disease while sparing normal tissue. The aim of this study was to use different methods to induce dendritic cells (DCs) derived from patients with CML (CML-DCs) and analyze them for CML-specific tumor cytotoxicity for immune therapy. Bone marrow-derived mononuclear cells from ten CML patients were studied to induce CML-DC differentiation in the presence of recombinant human interleukin-4, rh-granulocyte-macrophage-colony stimulating factor, and tumor necrosis factor-alpha with either a total RNA-lipofectamine complex, total RNA or CML tumor lysate (freeze-thawed). CML-DC maturation, confirmed by expression of CD1α, CD40, CD80, CD83, CD86 and by real-time polymerase chain reaction, validated the CML-origin of these DC cells. CML-DCs stimulated cytotoxic T-cell (CTL) apoptosis, high levels of IL-12 secretion, and had significant inhibitory effect on K562 tumorigenicity in nude mice. CML-DCs pulsed with total RNA by lipofectamine transfection produced the strongest effect in tumor-specific CTL functions. These results indicate that CML-DCs transfected with total RNA by lipofectamine induce the strongest CTL cytotoxicity and have the greatest potential for CML immune therapy. This study holds promise for a DC-based strategy for inducing anti-leukemia responses and establishes a foundation for developing RNA vaccination against CML.

[RNAi-mediated Silencing of CXCR4 Inhibits the Adhesion, Invasion and Tumorigenicity of Acute Monocytic Leukemic Cell Line SHI-1].

OBJECTIVE: To investigate the effect of CXCR4 gene on the proliferation, adhesion, invasion and tumorigenicity of a human monocytic leukemic cell line SHI-1. METHODS: The lentivirus vector silencing the expression of CXCR4 was constructed for infection of SHI-1 cells silencing expression of CXCR4 in SHI-1 cells. The expression of CXCR4, MMP-2 and MMP-9 was detected by real time PCR. The expression of CXCR4 on membrane of SHI-1 cells was detected by flow cytometry. The SHI-1 cell proliferation ability was detected by MTT. The co-culture system of the leukemia cells and bone marrow stromal cells was used to detect the adhesion and migration ability of leukemia cells. SHI-1 cells were inoculated subcutaneously in nude mice to investigate the growth ability in vivo. RESULTS: After SHI-1 cells were infected by lentivirus silencing expression of CXCR4, the expression of CXCR4 mRNA in SHI-1 CXCR-4i cells decreased by 76% as compared with expression of SHI-1/NC of negative control virus, the expression of CXCR4 on membrane of SHI-1/CXCR4i obviously downregulated; the expression of MMP-2 and MMP-9 in SHI-1/CXCRi cells also declined by 63% and 62% respectively; the proliferation ability of SHI-1/CXCR4i in vitro did not obviously changed, but the adhesion and trans-matrigel invasion ability significantly decreased, the SHI-1/CXCR4i cells could not form neoplasm subcutaneously in mice, but the SHI-1 and SHI-1/NC cells could form neoplasm subcutaneously in mice, and there was no significant difference in volumn of neoplasm mass. CONCLUSION: The silencing expression of CXCR4 can decline the adhesion and migration ability of SHI-1 cells, and can completely suppress the formation of neoplasm subcutaneously, so the CXCR4 may serve as a target for treating leukemia.

[Expression and significance of HSP90 in plasma of patients with multiple myeloma].

This study was purposed to investigate the expression of heat shock protein 90 (HSP90) in peripheral blood plasma of patients with multipl myeloma (MM), and to explore its possible role in the pathogenesis of MM, and its relationship with treatment, prognosis and the outcome of patients. The peripheral blood samples from 58 patients with MM and 20 healthy volunteers were collected. The plasma concentration of HSP90 in patients and healthy volunteers was measured by ELISA. The results showed that the concentration of HSP90 in peripheral blood of patients with MM was significantly higher than that in the healthy volunteers [(32.398 ± 3.674) vs (25.762 ± 2.916) ng/ml] (P < 0.001). The concentration of HSP90 showed positively correlation with International Staging System(ISS) stage, therapeutic response, frequency of plasmocyte, globulin, immune globulin, M-protein, ß2 micro-globulin, and light chain of MM patients (P < 0.05) ; while it showed little correlation with sex, age and type of MM patients (P > 0.05) . It is concluded that the HSP90 may be involved in the occurrence and development of MM. Detection of HSP90 in plasma would contribute to judge the clinical course, therapeutic efficacy and prognosis of MM patients.

[Expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura and its significance].

OBJECTIVE: To investigate the expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura (ITP) and its significance. METHODS: The quantity of CD4(+)CD25(+)T cells, CD4(+)CD25(high) T cells and CD4(+) IL-17(+)T cells in peripheral blood were measured with flow cytometry (FCM), the plasma level of IL-10 and IL-17 with ELISA and the expression of Foxp3 mRNA and RORc mRNA with RT-PCR in 29 newly diagnosed ITP patients and 28 healthy controls. RESULTS: The ratio of CD4(+)CD25(+)T cells/CD4(+) T cells in the peripheral blood of ITP patients was significantly higher than that of the normal controls (P < 0.05). And the ratio of CD4(+)CD25(high) T/CD4(+) T cells in the patients was remarkably lower (P < 0.05). There was no difference in the percentage of CD4(+) IL-17(+)T/CD4(+) T cells between ITP patients and controls (P > 0.05). The ratio of Treg/Th17 was lower in ITP patients (P < 0.05). The plasma level of IL-10 in ITP patients was significantly decreased (P < 0.05), whereas no statistical difference was observed in the level of IL-17 (P > 0.05). The Foxp3 mRNA expression levels were largely reduced (P < 0.05), but the RORc mRNA expression was increased compared with that in controls (P < 0.05). CONCLUSION: The imbalance of Treg/Th17 plays an important role in the pathogenesis of ITP.

N-acetyl cysteine inhibits human signet ring cell gastric cancer cell line (SJ-89) cell growth by inducing apoptosis and DNA synthesis arrest.

BACKGROUND AND AIMS: In this study, we investigated the inhibitory effects of N-acetyl cysteine (NAC) on the growth of the human signet ring cell from the gastric-cancer cell line SJ-89 , via the induction of apoptosis and the arrest of DNA synthesis. MATERIALS AND METHODS: SJ-89 cells were regularly incubated in the presence of NAC at 5, 10 and 20 mmol/l, and with IMDM as untreated control. Trypan blue-dye exclusion analysis and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay were applied to detect cell proliferation. Apoptotic morphology was observed by electron microscopy. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay were performed to detect NAC-triggered apoptosis. RESULTS: NAC could inhibit proliferation of human gastric cancer SJ-89 cells in a dose-dependent and time-dependent manner. The growth curve showed suppression by 15.8, 37.6 and 66.3% following 72 h of NAC treatment at 5, 10 and 20 mmol/l, respectively, similar to the findings of 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis was evidently reduced by 25, 39 and 91% after 24 h NAC treated at 20 mmol/l and 5 days at 10 and 20 mmol/l, respectively. Cell growth was inhibited by 100% with the treatment of 20 mmol/l NAC on day 6. NAC-treated SJ-89 cells were characterized by typical apoptotic alterations, including morphological changes by electron microscopy, typical apoptotic sub-G1 peaking observed by flow cytometry and increase of apoptotic cells with the elevation of the concentration of NAC in a clearly dose-dependent manner by TUNEL assay. Electrophoresis analysis showed typical 'DNA ladder'. CONCLUSION: The data above implicated that NAC inhibits human gastric-cancer SJ-89 cell growth by inducing apoptosis and DNA synthesis arrest. Although the exact mechanisms involved in NAC-induced apoptosis have not been known up to now, the ability to induce apoptosis in a tumor-cell population within 48 h is worth noting. It is also noteworthy that NAC can selectively inhibit the growth of tumor cells. Further studies are needed to elucidate the mechanisms.

[Treatment of chemotherapy-induced neutropenia pegylated recombinant human granulocyte colony-stimulating factor: a multi-center randomized controlled phase II clinical study].

OBJECTIVE: To compare the efficacy and safety of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), and a single subcutaneous injection of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), a sustained-duration rhG-CSF, in chemotherapy-induced neutropenia. METHODS: In the present randomized, open-label, match and cross-over study, enrolled 104 patients with previously untreated non-small cell lung cancer (NSCLC), breast cancer or non-Hodgkin's lymphoma and with normal bone marrow function from 13 centers were randomly divided into 2 matched groups, AB and BA group. Each patient received two cycles of chemotherapy of identical regimen. In the study cycle, the patients received a single subcutaneous injection of PEG-rhG-CSF 100 microg/kg on day 3; and in control cycle, daily subcutaneous infection of rhG-CSF 5 microg x kg(-1) x d(-1) began on day 3 and continued for 14 days or until the absolute neutrophil count (ANC) became > or = 5.0 x 10(9)/L twice after it decreased to the nadir. Efficacy and safety parameters were monitored. RESULTS: The incidence rates of ANC < 1.5 x 10(9)/L in the 103 evaluable study cycles and 100 evaluable control cycles were 30.00% and 20.00% with the duration of 2.39 days and 2.35 days respectively. The incidence rates of grade 3 neutropenia were 7.77% and 7.00%; and that of grade 4 neutropenia were 5.80% and 4.00% respectively in the trial and control cycles. However, all the difference mentioned above did not reached statistical significance. None of the patients experienced febrile neutropenia. The ANC nadir was (7.55 +/- 5.25) x 10(9)/L and (8.42 +/- 5.57) x 10(9)/L (P = 0.257) respectively after receiving PEG-rhG-CSF and rhG-CSF. Compared with that of rhG-CSF group, the ANC profile of PEG-rhG-CSF group exhibited limited "overshoot" of neutrophils after the nadir. Subgroup analysis according to disease type yielded similar results. The safety profiles of the PEG-rhG-CSF and rhG-CSF groups were similar. Musculoskeletal pain or arthralgia occurred in 16.5% of the study cycles and 26.00% of the control cycles (P = 0.963), mostly mild or moderate. Other adverse effects such as fever, fatigue, dizziness, gastrointestinal effects and injection-site pain, were transient and easily manageable. CONCLUSION: A single subcutaneous injection of PEG-rhG-CSF 100 microg/kg provides neutrophil support and a safety profile comparable to regimen of daily subcutaneous injection of rhG-CSF 5 microg x kg(-1) x d(-1) in Chinese patients receiving a variety of myelosuppressive chemotherapy regimens.