LRP5 polymorphism-A potential predictor of the clinical outcome in advanced gastric cancer patients treated with EOF regimen.

PURPOSE: Wnt pathways control key biological processes that potentially impact on tumor progression and patient survival. The present study analyzed the polymorphism of lipoprotein-related receptor 5 (LRP5) (gene with key functions in Wnt signaling) and its impact on the response to chemotherapy and survival of patients with advanced gastric cancer (AGC). METHODS: A total of 107 consecutive patients with AGC treated with first-line chemotherapy of EOF regimen were enrolled in the present retrospective study. The association between single nucleotide polymorphism (SNP) of rs3736228 in LRP5 and the clinical outcomes of the patients was studied. RESULTS: The CC genotype of rs3736228 was significantly correlated with a higher disease control rate when compared to the CT and TT genotypes (89.3% and 61.8%, respectively, P<0.001). A univariate survival analysis also showed that the progression free survival (PFS) and overall survival (OS) for the patients with the TC and TT genotypes of rs3736228 were worse than for the patients with the CC genotype (PFS: 3.3 and 6.7 months, respectively, HR =0.454, P<0.001; OS: 8.1 months and 18.8 months, respectively, HR =3.056, P<0.001). A multivariate Cox model incorporates rs3736228 and clinical features, also identified rs3736228 was significantly associated with the PFS and OS. CONCLUSIONS: Our results firstly highlight the importance of LRP5 gene of Wnt pathway in the treatment of AGC and identify polymorphism of rs3736228 as independent predictor of disease control rate, PFS and OS in AGC patients treated with first-line chemotherapy of EOF regimen in the Chinese Han population.

Chloroxoquinoline in combination with epirubicin, cisplatin and 5-fluorouracil in metastatic gastric cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and tolerability of combination chemotherapy with epirubicin, cisplatin, 5-fluorouracil (ECF regimen), and Chloroxoquinoline in patients with metastatic gastric cancer. METHODOLOGY: Twenty-two patients with histologically confirmed metastatic gastric adenocarcinoma were treated with a combination of epirubicin 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 1), 5-fluorouracil 500 mg/m2 (days 1 to 5), and Chloroxoquinoline 400 mg (days 1 to 21), with the cycle repeated every three weeks. RESULTS: Twenty patients were evaluable for response. One case of (5%) complete response, seven of (35%) partial response, nine (45%) of stable disease, and three (15%) of progressive disease were observed, giving an overall treatment response rate of 40%. Median survival time was 9.4 months, median progression-free survival was 6.1 months, and the 1-year survival rate was 25%. Both hematologic and non-hemotologic toxicities were well tolerated and no treatment-related deaths occurred. In patients who received Chloroxoquinoline maintenance monotherapy after six cycles of the combination regimen, progression-free survival was nine months. CONCLUSION: The combination regimen demonstrated comparable efficacy and acceptable safety profiles in patients with metastatic gastric cancer. Chloroxoquinoline maintenance monotherapy has a tendency to increase progression-free survival.

[Clinical significance in detection of immunoglobulin heavy chain clonal rearrangement in bone marrow of patients with B cell lymphoma].

OBJECTIVE: To explore the feasibility of semi-nested PCR technique for detection of immunoglobulin heavy chain (IgH) clonal rearrangement in bone marrow of B-cell lymphoma patient and to further evaluate its clinicopathological value. METHODS: Gene clonal rearrangement of IgH was detected by semi-nested PCR using primers of FR2 & FR3A in 105 bone marrow samples of patients with B-cell lymphoma. The PCR detection results were compared with the cytomorphology of bone marrow aspiration biopsy. The correlation between PCR detection results and clinicopathological factors were evaluated. RESULTS: Among 105 cases of B-cell lymphoma, bone marrow involvement was detected by PCR technique in 48 cases (45.7%), while only 22 cases (21.0%) were detected by bone marrow cytological analysis. There was a significant difference between two methods (P < 0.05), and the concordance rate was 71.4%. The incidence of bone marrow involvement at the time of initial diagnosis detected by PCR technique was 30.8% for diffuse large B cell lymphoma (DLBCL), 25.0% for follicular lymphoma (FL), and 100.0% for small lymphocytic lymphoma (SLL), respectively. Bone marrow involvement detected by PCR detection correlated with Ann Arbor stage. Rate of clonal IgH gene rearrangement by PCR in early B-cell lymphoma was lower than that in advanced stage B-cell lymphoma patients (P = 0.02). There was no statistically significant difference in efficacy between patients with positive and negative results detected by PCR (P > 0.05). But difference in complete response (CR) rate (23.3% and 46.3%) had significant difference (P = 0.019). CONCLUSION: Semi-nested PCR analysis may be an effective method for detection of abnormalities in bone marrow in patients with B-cell lymphoma and is superior to cytomorphology. The positive rate in patients with advanced Ann Arbor stage is higher than that in patients with early Ann Arbor stage, and patients with PCR negative result have more chances to achieved CR after treatment.

[Prognosis of primary non-Hodgkin's lymphoma of the breast].

OBJECTIVE: To analyze the clinical characteristics and prognosis of primary non-Hodgkin's lymphoma of the breast (PNHLB). METHODS: The characteristics, treatment methods and outcomes of 45 patients with PNHLB were retrospectively analyzed. Chemotherapy including CHOP and CHOP-like regimens was administered in 43 patients, and monoclonal antibody therapy in 6 patients. Furthermore, 19 patients underwent radiotherapy after chemotherapy. RESULTS: Of these 45 patients, 37 patients had diffuse large B cell lymphoma (DLBCL), patients with T cell or mucosa-associated lymphoid tissue (MALT) lymphoma were 4, respectively. Overall response rate of first-line chemotherapy was 90.7%. Median overall survival (OS) and progression-free survival (PFS) of all patients was 6.82 and 4.25 years, respectively. The results of Cox regression model analysis showed that international prognostic index score (IPI) (RR = 5.682, P = 0.002) and Ann Arbor stage (RR = 1.836, P = 0.040) were negative independent prognostic factors for OS. Central nervous system involvement (RR = 1.107, P = 0.005) was a negative independent prognostic factor for PFS. CONCLUSION: The patients with PNHLB have early occurrence in lifespan. Most pathologic type was DLBCL. IPI and Ann Arbor stage are two independent prognostic factors for survival.

[Prognostic predictors of nasal NK/T cell lymphoma detected by immunohistochemical staining].

OBJECTIVE: To investigate the prognostic predictors of nasal NK/T cell lymphoma. METHODS: The clinicopathologic feature data of 61 patients with nasal NK/T cell lymphoma proven by pathological examination from Jan. 1997 to Jan. 2005 were collected. Expression of survivin, CD44, nm23, p53, Ki-67, MDR-1 and CD95 was detected by immunohistochemical staining in 30 patients with available histologic specimens. The correlation between these factors and prognosis were analyzed. RESULTS: In univariate analysis, performance status, LDH level, clinical stage, initial treatment response, CD56, Ki-67 and CD95 were found to be the prognostic factors associated with time to progression (TTP) in nasal NK/T cell lymphoma, while the performance status, B symptoms, LDH level, initial treatment response, Ki-67 and CD95 were demonstrated as prognostic factors related to overall survival. In multivariate analysis, clinical stage, initial treatment response and performance status were independent prognostic factors for TTP, while the latter two factors were independent prognostic factors of overall survival. CONCLUSION: Clinical stage and initial treatment response, and performance status are found to be independent prognostic factors for TTP, whereas the latter two factors are demonstrated as independent prognostic factors of the overall survival. Overexpression of Ki-67 may be an unfavorable prognostic factor, but overexpression of CD95 may be a favorable one.

[Vinorelbine plus cisplatin in the treatment of advanced non-small cell lung cancer previously treated with taxane-based chemotherapy].

OBJECTIVE: To evaluate the efficacy and toxicity of vinorelbine plus cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC) previously treated with taxane-based chemotherapy. METHODS: Thirty patients (0 - 1 score ECOG performance status) with stage IIIB/IV NSCLC previously treated with taxane-based chemotherapy were eligible for the study. Fifteen patients received the regimen of vinorelbine plus cisplatin (NP), the others received mitomycin, vindesine plus cisplatin (MVP). RESULTS: The overall response rates were 13.3% in NP and 0 in MVP (P > 0.05). Time to progression was longer for NP patients than that for MVP ones (6 v 3 months, P < 0.05), so was median survival (9 v 6 months, P < 0.05). The 1-year survival rate of 40.0% in the NP group was significantly higher than that of 0 in MVP (P < 0.05). Grade III-IV toxicity was observed at a similar rate in both groups (P > 0.05), though both well tolerated. CONCLUSION: Regimen of vinorelbine plus cisplatin is appropriate for good performance status patients with advanced non-small cell lung cancer previously treated with taxane-based chemotherapy. Time to progression, median survival and 1-year survival are satisfactory in patients treated with NP, which is complicated with acceptable toxicity.

[Result of phase II clinical trial of herceptin in advanced Chinese breast cancer patients].

OBJECTIVE: To observe the clinical efficacy and adverse effects of herceptin for advanced Chinese breast cancer patients. METHODS: Thirty-one pathologically proved advanced breast cancer women were treated by herceptin. In the first week, a loading dose 4 mg/kg was administered by intravenous infusion and from the second week, a routine dose of 2 mg/kg was given every week for at least 3 months. RESULTS: There were 2 CR, 6 PR, 7 SD, and 16 PD among 31 patients after treatment by herceptin, the response rate being 25.8%. In factors influencing the prognosis, age and general condition were factors favoring the results, and pathological type, site of metastasis, grade of her-2 over expression and prior treatment were irrelevant to the results. The adverse effects were mild but different from those of the common anticancer drugs. CONCLUSION: Herceptin is effective and well tolerated by the Chinese breast cancer patients.

Intensive chemotherapy failure in Burkitt's lymphoma with cavernous sinus involvement.

Burkitt's lymphoma is an aggressive B-cell lymphoma with rapid proliferative index, which makes it disseminate easily to distal sites, especially to bone marrow and the central nerve system. We report here a 22-year-old woman with Burkitt's lymphoma involving multiple organs, including kidneys, breasts, left ovary, and bone marrow at the time of diagnosis. The patient responded well to intensive chemotherapy before the onset of retro-orbital pain, vomiting, and photophobia. The contrast-enhanced T1-weighted image in a second magnetic resonance image (MRI) showed a 2 x 1.9 cm mass in her left cavernous sinus that was not found in her initial MRI. Central nervous system (CNS)-directed high-dose chemotherapy and whole-brain radiation could not change the final failed treatment outcome caused by the cavernous sinus involvement disseminating to her entire CNS. Further study should provide well-designed therapeutic strategies to Burkitt's patients with cavernous sinus involvement.