ABSTRACT: ObjectiveIt remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use. This trial was designed
to explore efficacy and safety of sequential vs simultaneous use of vinorelbine and capecitabine at the same dosage as first-line
therapy in metastatic breast cancer (MBC).
MethodsThis was a un-icenter, randomized phase II trial. Patients randomized into the simultaneous group (group A) were simultaneously
administered with vinorelbine and capecitabine while those in the sequential group (group B) received vinorelbine followed
by capecitabine at the same dosage.
ResultsSixty-six patients were screened and 30 patients were randomized into either group. There’re significant differences in the
clinical benefit rate (CBR) with 80.0% for group A vs 53.3% for group B (P = 0.028). With a median follow up time of 13.5 months, there were no significant differences between the two groups in PFS
(median PFS: 7.70 months for group A vs 7.23 months for group B, P = 0.436). Grade III or IV neutropenia (83.3% vs 50.0%, P = 0.006), all grades of fatigue (56.7% vs 30.0%, P = 0.037) and anorexia (53.3% vs 23.3%, P = 0.017) were significantly more frequent in simultaneous group.
ConclusionSimultaneous administration of vinorelbine and capecitabine can bring about improvements in CBR, but cannot translate into
long-term benefits, such as progression-free survival (PFS) or overall survival (OS). These findings, combined with a relatively
better tolerability in sequential group, showed that both simultaneous and sequential administrations are reasonable options
for MBC patients.
Key wordsvinorelbine-capecitabine-simultaneous administration-sequential administration-metastatic breast cancer (MBC)-phase II clinical trial
The Chinese-German Journal of Clinical Oncology 04/2012; 9(9):528-535.
ABSTRACT: ObjectiveThe mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to
anthracyclines, vinorelbine and taxanes.
MethodsThree-weekly regimen consisted of mitomycin, 6 mg/m2 administered intravenously on day 1, and cisplatin, 25 mg/m2 intravenously on day 1–3.
ResultsThirty-eight patients aged 25–75 years (median, 46 years) were treated with an overall response rate of 31.6%. The median
time to progression (TTP) was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while
stable disease and progression of disease 4.0 months, P=0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 (10.5%), 4 (10.5%)
and 3 (7.9%) patients, respectively. The median overall survival was 13+ months.
ConclusionMitomycin C/cisplatin doublet showed antitumor activity for anthracycline-, vinorelbine-and taxane-resistant breast cancer
comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China.
The Chinese-German Journal of Clinical Oncology 04/2012; 5(6):442-445.
ABSTRACT: To assess prognostic and predictive effects of clinical and biochemical factors in our published randomized study of a weekly low dose (metronomic arm) versus a conventional dosage of zoledronic acid (conventional arm) in breast cancer patients with bone metastases.
Treatment outcome of 60 patients with bone metastases were used to assess impacts of following potential prognostic factors, estrogen receptor status, lymph node status, 2 year-disease free interval (DFI), numbers of chemotherapy regimens administered, interventions, and serum levels of VEGF, N-telopeptide of type I collagen (NTx), CEA, and CA 15-3.
In univariate analyses, patients pretreated with 2 or fewer chemotherapy regimens, ER-positive tumors, 3 or fewer lymph nodes, DFI of more than 2 years, serum VEGF of less than 500 pg/mL after 3 months of intervention, serum CEA and CA 15-3 of less than ULN, and baseline serum NTx of less than 18 nM BCE had significantly longer progression free survival (PFS). The multivariate analysis showed that ER positivity (hazard ratio [HR], 0.295; 95% confidence interval [CI], 0.141-0.618; P = 0.001), serum VEGF of less than 500 pg/mL after 3 months of intervention (HR, 2.220; 95% CI, 1.136-4.338; P = 0.020), baseline serum NTx of less than 18 nM BCE (HR, 2.842; 95% CI, 1.458-5.539; P = 0.001), and 2 or fewer chemotherapy regimens received (HR, 7.803; 95% CI, 2.884-21.112; P = 0.000) were associated with a better PFS. When evaluating the predictive effect of the biochemical factors, an interaction between NTx and zoledronic acid intervention was shown (P = 0.005). The HR of weekly low dose versus a conventional dosage of zoledronic acid was estimated to be 2.309 (99% CI, 1.067-5.012) in patients with baseline serum NTx of more than 18 nM BCE, indicating a superiority of weekly low dose of zoledronic acid.
ER, serum VEGF level after intervention, and numbers of chemotherapy regimens administered are prognostic but not predictive factors in breast cancer patients with bone metastases. Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid.
ClinicalTrials.gov unique identifier: ClinicalTrials.gov: NCT00524849.
BMC Cancer 09/2011; 11:403. · 3.01 Impact Factor
ABSTRACT: YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies.
This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death.
Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks.
The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations.
ClinicalTrials.gov unique identifier: NCT00633490.
BMC Cancer 10/2010; 10:529. · 3.01 Impact Factor
ABSTRACT: Zoledronic acid has direct and indirect antitumor effects. However, the optimal regimen for breast cancer patients remains to be determined. This study aimed to compare biomarker changes between a weekly low dose (metronomic arm) and a conventional dosage of zoledronic acid (conventional arm), and to explore correlations between biomarkers and progression-free survival (PFS). Sixty breast cancer patients with bone metastases were randomized to receive either zoledronic acid 1 mg IV weekly for 4 doses or a single dose of zoledronic acid 4 mg IV. Administration of other treatments was delayed for 1 month. Serial blood samples were collected on days 1, 15, 29, and at 3 months. Serum VEGF alteration was the primary endpoint. Compared to the conventional arm, the metronomic arm resulted in a significantly greater reduction in serum levels of VEGF and N-telopeptide of type I collagen (NTx) over time during the first month of treatment. Serum CA 15-3 level stabilized over time in the metronomic arm, but increased in the conventional arm. Independent prognostic factors for PFS included chemotherapy received (HR, 8.042; P = 0.000), estrogen receptor status (HR, 2.837; P = 0.020), VEGF levels at 3 months after intervention (HR, 2.026; P = 0.045), and baseline NTx (HR, 1.051; P = 0.001). Metronomic low-dose zoledronic acid is more effective than the conventional regimen and generates sustained reductions in circulating VEGF and NTx levels, as well as stabilization of serum CA 15-3 levels (ClinicalTrials.gov number, NCT00524849).
Breast Cancer Research and Treatment 09/2010; 124(3):733-43. · 4.43 Impact Factor
ABSTRACT: The dosing schedule of docetaxel may affect its clinical activity and toxicity profile. Although triweekly docetaxel has higher antitumor activity but more severe hematological toxicity, weekly docetaxel seems to have less activity or fewer adverse events. To evaluate the efficacy and toxicity of biweekly docetaxel and mitoxantrone in patients with advanced breast cancer, the regimen consisting of docetaxel (60 mg/m), and mitoxantrone (8 mg/m) was administered intravenously to 59 patients every 2 weeks. Most (54.2%) of the patients experienced objective responses. The median time to progression for the whole group was 6.8 months. The median time to progression for patients with complete or partial response was 10.3 months, but only 3.6 months for patients with stable or progressive disease (P<0.001). Grade III/IV adverse events of neutropenia, thrombocytopenia, anemia, febrile neutropenia, and nausea/vomiting were documented in 61.0, 6.8, 3.4, 3.4, and 3.4% of the patients, respectively. The median overall survival was 16.9 months. In conclusion, biweekly use of docetaxel and mitoxantrone is a highly effective and well-tolerated regimen for patients with advanced breast cancer. The optimal dosage of docetaxel in combination with chemotherapeutic regimen may be given every 2 weeks.
Anti-Cancer Drugs 04/2008; 19(4):421-6. · 2.41 Impact Factor
ABSTRACT: There is no gold standard to treat primary gastric non-Hodgkin's lymphoma (PG-NHL). Hence, the establishment of effective prognostic factors of PG-NHL is essential for its staging and management.
We retrospectively analyzed the clinicopathological features of PG-NHL patients who had been diagnosed from 1990 through 2008 in a Chinese cancer center. Event-free survival (EFS) and overall survival (OS) were primary endpoints.
Estimated EFS and OS rate at 5 years were 76.0% and 78.7%, respectively. Log-rank analyses revealed OS was significantly prolonged by the following factors: age < or = 60 years; histology of mucosa-associated lymphoid tissue lymphoma; performance status of 0-1; modified Ann Arbor stage IE or IIE1 disease; normal lactic dehydrogenase level; normal hemoglobin level; normal albumin level; International Prognostic Index of 0 or 1; tumor size < or = 5 cm; and less depth of invasion. Only performance status, modified Ann Arbor stage and albumin level retained their significance for EFS and OS in the multivariate analysis.
We strongly recommend including albumin level in the management of Chinese patients. Further randomized studies with a large number of cases are needed to establish the optimal management for this disease.
Hepato-gastroenterology 57(101):989-96. · 0.66 Impact Factor