Triplet chemotherapy combination with cisplatin, gemcitabine and docetaxel in patients with chemotherapy-naive advanced non-small cell lung cancer.

The synergistic effects of new generation chemotherapeutics when combined with cisplatin have encouraged the development of new triplet combination regimens in the treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of triplet chemotherapy using weekly cisplatin-gemcitabine-docetaxel (CGD) for patients with chemotherapy-naive NSCLC. Twenty-seven patients with stage IIIB/IV disease and performance status of 0 to 2 were included in this prospective trial. A combination of gemcitabine 750 mg/m2, cisplatin 25 mg/m2 and docetaxel 25 mg/m2 was administered on days 1, 8 and 15, with cycles repeated every 3 weeks. Leucopenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Grade III-IV neutropenia and thrombocytopenia occurred in 26 and 7% of the patients, respectively. Only one patient developed febrile neutropenia. Dose reductions were required in 26% of patients, delays in 44% of patients and early treatment discontinuation in 15% of patients. The overall response rate was 52% and all of them experienced a partial response. The median progression-free (PFS) and overall survival (OS) times were 6 and 13 months, respectively. The one-year survival rate was 46%. In conclusion, weekly administration of CGD is an active first-line therapy with acceptable toxicity in advanced NSCLC patients.

Utility of serum and urine uPAR levels for diagnosis of breast cancer.

Malignant tumors have a capacity to degrade the extracellular matrix by controlled proteolysis. One system involved in these processes is the urokinase-type plasminogen activator (uPA) system. uPAR levels are elevated in tumors from several types of cancer. Our study was planned to investigate serum and urine levels of uPAR in breast cancer patients (n=180) and healthy controls (n=60) by ELISA. Serum (p<0.001) and urine (p<0.001) uPAR values in the patients were both significantly elevated. High serum and urine levels of uPAR can be used as diagnostic tools in lymph node positive patients.

Serum levels of interleukin-6 and interleukin-10 in Turkish patients with aggressive non-Hodgkin's lymphoma.

There exists strong evidence that tumor growth can be actively controlled by the host immune system and interleukins are known to play a significant role in immune response regulation. Inflammatory cytokines play important roles in the pathogenesis of lymphomas. This study was conducted to investigate the serum levels of IL-6 and IL-10 in patients with aggressive non-Hodgkin's lymphoma (A-NHL) and the relationships with prognostic parameters and therapy. These serum factors were measured in 46 A-NHL patients pathologically verified before and after chemotherapy in comparison with 21 healthy controls using enzyme-linked immunosorbent assays (ELISAs). There were significant differences in the serum IL-10 and IL-6 levels between A-NHL patients and controls (p= 0.038 and p<0.001, respectively). None of the prognostic parameters analyzed was significantly correlated with the serum IL-6 concentrations. This was also true for serum IL-10 values, except for LDH and bone marrow involvement. Serum IL-10 levels were elevated in the group of patients with high level LDH compared with the group of patients with a normal level (p= 0.017). Also, serum IL-10 levels were significantly different in the presence or absence of bone marrow involvement (p= 0.016). In addition, we found a significant relationship between the serum levels of serum levels of IL-6 and IL-10 in patients with A-NHL (r= 0.47, p<0.001). We found that serum IL-10 levels decreased due to chemotherapy effect independent of the chemotherapy response (p= 0.027). However, serum IL-6 levels were not changed. In conclusion, our data suggest that higher serum IL-6 and IL-10 levels can be useful for diagnosis of A-NHL. However, our sample size is small, and larger scale research is needed in this field to provide new knowledge.

Yolk sac tumours of the ovary: evaluation of clinicopathological features and prognostic factors.

OBJECTIVE: To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST). STUDY DESIGN: We reviewed the medical records of 32 women with ovarian YST treated from 1990 to 2006 at two centres. RESULTS: The median follow-up was 36 months. The median age was 22 (range, 9-68). Two patients were postmenopausal. The most common symptoms at diagnosis included abdominal swelling or mass (72%) and abdominopelvic pain (62%). The location of the tumour was bilateral in 2 cases. Eight patients were in stage I, 4 patients in stage II, 17 patients in stage III, and 3 patients in stage IV. Eighteen patients underwent unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two cystectomy, while 10 patients had total abdominal hysterectomy and two bilateral salpingo-oophorectomy. Of 32 patients who received postoperative chemotherapy, 27 were treated with a bleomycin/etoposide/cisplatin (BEP) regimen. Seventy-two percent of patients were alive at the last follow-up visit. Ten (31%) patients suffered from a recurrence of the disease with a median time to recurrence of 8 months (range, 6-28 months). The most common site of recurrence was the intra-abdominal space, with 8 patients. Only one patient who had recurrence could be salvaged. Fertility-sparing surgery was found at least as effective as radical surgery. While age, histology (mixed vs. pure), stage, tumour size, ascites, and marker levels were not found as prognostic factors, the presence of residual tumour (P=0.014) and BEP chemotherapy (P=0.016) were significant prognostic factors in univariate analysis. CONCLUSIONS: In patients with ovarian YST, fertility-sparing surgery is as effective as radical surgery. Optimal cytoreductive surgery and standard BEP regimen are the most decisive prognostic factors. In these tumours, adjunctive therapeutic modalities to eradicate intra-abdominal disease and effective salvage therapy strategies are needed.

Risk-adapted management for patients with clinical stage I non-seminomatous germ cell tumour of the testis.

Testis cancer is the most common cancer in young men and its incidence continues to rise. Even if prognosis is considered as good, a group with bad prognosis still remains. We aimed to evaluate whether two courses of chemotherapy after orchiectomy in patients with clinical stage I, non-seminomatous germ cell testicular tumour at high risk of relapse, will spare patients additional chemotherapy or surgery. High-risk patients had one or more of the following: preorchiectomy alpha-fetoprotein level of 80 ng/dl, 80% embryonal cell carcinoma or greater, vessel invasion in the primary tumour and tumour stage pT2 or greater. Low-risk patients had none of these factors or had 50% teratoma or more without vessel invasion. High-risk patients were offered two 21-day courses of outpatient chemotherapy consisting cisplatin, etoposide and bleomycin (BEP). Low-risk patients were observed. Of the 108 patients, we classified 71 as high risk and 37 as low risk of relapse. All of the high-risk patients received two courses of BEP chemotherapy. Low-risk patients were kept on close-up. The median follow-up was 26 months (range 10-60). Of the 71 patients in high-risk group, 3 relapsed with viable cancer and required additional chemotherapy and 1 patient with normal biomarkers and a late-appearing mass underwent retroperitoneal lympadenectomy for mature teratoma. All 4 relapsed patients were in high-risk group and presently they are free of disease. None of the 37 patients at low risk of recurrences developed relapse. We recommend two courses of adjuvant chemotherapy after postorchiectomy for high-risk patients with stage I non-seminomatous germ cell tumour of the testis. Adjuvant chemotherapy for these patients results in a low relapse and morbidity, wich compares favourably with the results of surveillance or RPLND. This well-tolerated approach may spare patients additional surgery or protracted chemotherapy, reduce the cost and eliminate the compliance problems associated with intensive follow up of high-risk patients.

Chemotherapy with pegylated liposomal doxorubicin and cisplatin in recurrent platinum-sensitive epithelial ovarian cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients. METHODS: Twenty-two women (median age, 57 years) with ovarian cancer that recurred 6 months or more after standard carboplatin and paclitaxel therapy were eligible for enrollment. Cisplatin was administered intravenously as a 60-min infusion on day 1, at a single dose of 60 mg/m(2), and PLD was given intravenously as a 1-h infusion on day 2, at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. RESULTS: Hematological toxicity was mainly leucopenia/neutropenia, and this was the principal dose-limiting toxicity. Severe (grade III-IV) leucopenia/neutropenia was observed in 7 (32%) and 9 (41%) patients, respectively. Only 2 (9%) patients were complicated by febrile neutropenia. Grade III-IV anemia occurred in only 4 (18%) patients. Severe thrombocytopenia was not noted; only 5 patients (23%) had grade I-II toxicity. NO toxicity in biochemical parameters was noted. Several severe nonhematological adverse effects were managed according to standard protocols and were transient, as well as being well-tolerated. Twenty-one patients were evaluated for response. The overall response rate was 62% (13 of 21; 95% confidence interval [CI], 38%-82%), with four (19%) complete and nine (43%) partial responses. At the time of last follow-up, all of the 22 patients were alive. The median follow-up period was 8.5 months (range, 2 to 22 months). CONCLUSION: PLD combined with cisplatin at the schedule and dosage used in this study is an active and safe second-line chemotherapy regimen with acceptable and easily manageable toxicities in women with platinum-sensitive recurrent ovarian cancer.

Lower level of MAPK expression is associated with anthracycline resistance and decreased survival in patients with hormone receptor negative breast cancer.

INTRODUCTION: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer. METHODS: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival. RESULTS: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04). CONCLUSION: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer.

BACKGROUND: Both gemcitabine and pegylated liposomal doxorubicin (PLD) are antineoplastic drugs with clinical activity in patients with platinum-resistant ovarian cancer. The present study was designed to assess the efficacy and safety of biweekly scheduled gemcitabine and PLD combination therapy in such patients. METHODS: Eighteen women with ovarian cancer that had recurred within 6 months after standard carboplatin and paclitaxel therapy were eligible for enrollment. Gemcitabine 2000 mg/m(2) and PLD 20 mg/m(2) were administered intravenously on days 1 and 15 of a 28-day cycle. RESULTS: Hematological toxicity was mild. No severe (grade III/IV) leucopenia/neutropenia or thrombocytopenia was observed. Severe anemia was seen in only 3 (17%) patients. Several other severe nonhematological adverse effects were well tolerated and easily managed. The overall response rate was 28% (5 of 18; 95% confidence interval [CI], 10%-54%) with 2 (11%) complete and 3 (17%) partial responses. The median overall survival time was 17 months (range, 1 to 25 months). The median survival for patients with clinical benefit including disease response or stabilization was 17 months (range, 3 to 26 months) compared to that of patients with progressive disease, which was 2 months (range, 1 to 11 months; P = 0.04). CONCLUSION: A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer.

Ovarian carcinoma with simultaneous breast and rectum metastases.

BACKGROUND: Metastatic involvement of the breast and the rectum from ovarian carcinoma are very rare events. CASE REPORT: We report a case of ovarian carcinoma with metastasis to the breast and rectum simultaneously, 6 years after initial diagnosis. RESULTS: Morphologic and immunohistochemical findings from pathologic samples of all involved sites confirmed the ovarian origin, which spared the patient unnecessary breast and rectal surgery. To our knowledge, this is the first case of ovarian carcinoma with simultaneous metastases to the breast and rectum reported to date. CONCLUSION: Accurate differential diagnosis from primary breast and rectal carcinoma is very important because the prognosis and treatment differ significantly.

Ta T1 low and intermediate transitional cell carcinoma of the bladder: recurrence rates and the timing of check cystoscopies within the first year.

INTRODUCTION: The intensity of cystoscopic follow-up in the first year for patients with superficial bladder cancer has not been clearly defined. The cystoscopic follow-up of superficial bladder cancer accounts for a considerable workload for the urologist and is also an invasive procedure with high costs. We retrospectively reviewed our experience to determine any possible criteria which can lead to reduce the frequency of check cystoscopy. MATERIAL AND METHODS: A retrospective study was done on 427 patients with primary stage Ta and T1 bladder cancers treated between 1998 and 2005. The pattern of recurrence in the first year was assessed and recurrence rates calculated. RESULTS: The recurrence rate was 22% at 3 months. The recurrence rates at 6 and 9 months were 8 and 13.6% respectively. The recurrence rate at 12 months was 9.4%. For tumors with no recurrence at 3 months, the recurrence rates at 6, 9 and 12 months were 6.6, 13.4 and 8.9% respectively. With respect to stages, there was a statistically significant difference in recurrence rate stages pTa and pT1 in the first and in the third control (p = 0.001, p = 0.003) respectively. According to the recurrence rate within the first year, the difference between G1 and G2 tumors was not statistically significant regardless of the stage (p > 0.05). CONCLUSIONS: Patients with initial stage Ta or T1 grade 1 and 2 bladder cancers and negative first cystoscopy have a significantly lower recurrence rate than those with recurrence at first cystoscopy. There is a reason to change follow-up routines but in our opinion only in patients with initial low-grade carcinoma. If the third-month cystoscopy is clear, it is appropriate to perform the first check cystoscopy 1 year after initial resection.

Biweekly administration of gemcitabine and cisplatin chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer.

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n = 2) and renal toxicity (n = 1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily. Permanent dose reductions were necessary in 9 (33%) patients and chemotherapy administration was also delayed in 7 (26%) patients because of delayed both hematological and non-hematological toxicity recovery. Treatment was discontinued in one (4%) patient due to severe fatigue and deteriorating performance status. In conclusion, gemcitabine and cisplatin combination therapy with this biweekly schedule and dosage is moderately active and extremely safe in patients with metastatic breast cancer previously treated with anthracycline and taxanes.

Serum levels of intercellular adhesion molecule ICAM-1 and E-selectin in advanced stage non-small cell lung cancer.

Cell adhesion is a basic count in inter- and intra-cellular communication and plays an important role in tumor progression. This study was conducted to investigate the serum levels of intercellular adhesion molecule (ICAM-1) and E-selectin in patients with advanced stage non-small cell lung cancer (NSCLC) and the relationships with known prognostic parameters and therapy. These serum factors were measured of 57 NSCLC patients pathologically verified before and after chemotherapy in comparison with 24 healthy controls by using ELISA method. Serum levels of ICAM-1 were increased significantly in NSCLC patients compared with the healthy controls (P = 0.006). However, serum E-selectin levels were not significantly different from healthy control groups (0.643). No statistically significant relationships were found between investigated all serum parameters and various characteristics of patients, and the diseases such as stage and tumor burden. Likewise, we also found no correlation between serum ICAM-1 and E-selectin (P = 0.78). We found that serum ICAM-1 levels were decreased owing to the chemotherapy effect, independently from chemotherapy response. However, serum E-selectin levels were not changed by the chemotherapy effect. The median survival of all patients was 11.9 months and 1-year survival rate was 47.6%. We found that patients performance status (P = 0.013), age (P = 0.015), and weight loss (P = 0.007) were prognostic factors for survival. Serum E-selectin levels showed a trend (P = 0.08) related to worse prognosis, however serum ICAM-1 levels were determined as ineffective on survival (P = 0.11). Multivariate analysis revealed that only weight loss (P = 0.005) and E-selectin levels (P = 0.002) remained as an independent prognostic factor for survival in patients with advanced NSCLC. In conclusion, our data suggest that higher serum ICAM-1 can be useful for diagnosis while E-selectin levels have prognostic significance and could be a potential prognostic factor in NSCLC patients.

Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer.

CONTEXT: This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum apoptosis biomarkers consisting of survivin and tumor necrosis factor alpha (TNF-alpha) in patients with advanced stage nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Fifty-seven patients with newly diagnosed NSCLC were enrolled into study. Performance status was 0 or 1 in 47 patients and 2 in 10 patients. Thirty-two of them were no or less than 10% weight loss. Patients were treated with platinum-based chemotherapy. Serum levels of TNF-alpha and survivin were determined by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: While serum survivin levels in patients were not significantly different from controls (p=0.321), serum TNF-alpha levels in patients were found significantly higher than in controls (p=0.029). We found that serum TNF-alpha levels were increased (p<0.001), whereas serum levels of survivin (p=0.025) were decreased by the chemotherapy effects. The changes of the TNF-alpha and survivin serum levels due to chemotherapy effect showed a significant negative correlation (r=-0.36 p=0.007). The increase of serum TNF-alpha levels was independent from chemotherapy response; however, the reduction of serum survivin levels was found only significant in the chemoresponsive group (p=0.039). While older age, weight loss and performance status yielded prognostic value, neither TNF-alpha nor survivin levels proved to be significant for survival. CONCLUSION: Our findings suggest that the reduction in the serum survivin levels of advanced NSCLC patients after chemotherapy can be used as a predictor of response to the chemotherapy but not that of survival.

Malignant mesothelioma of the tunica vaginalis testis: a case report and review of the literature.

Most often, mesotheliomas involve the serosal membranes of the pleura and peritoneum. Sometimes, mesothelial proliferations are identified in other locations. A mesothelioma, within the tunica vaginalis of the paratesticular region is rare but often fatal malignancy of the male genitalia. Despite aggressive surgical and systemic therapy the prognosis remains poor with only rare long-term survivors. We report a case of malignant mesothelioma of the tunica vaginalis in 45-years-old and review of the literature is presented.

Serum IL-8 and IL-12 levels in breast cancer.

Interleukins (ILs) are known to play a fundamental role in cancer. We investigated the serum levels of IL-8 and IL-12, in breast cancer patients, and their relationship with the prognostic parameters and therapy. Forty eight patients with pathologically verified breast carcinoma and 21 healthy controls were enrolled into the study. Serum samples were obtained at baseline and after two cycles of chemotherapy. Serum IL-8 and IL-12 levels were determined using enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the baseline serum IL-8 and IL-12 levels between breast cancer patients and healthy controls (p = 0.365 and p = 0.871, respectively), no significant correlation between the prognostic parameters and the serum IL-8, IL-12 levels. However, in the subgroup consisting of metastatic breast cancer patients, baseline serum IL-8 levels were significantly higher compared with non-metastatic disease (p = 0.047). Anthracycline-based chemotherapy and the addition of taxane did not change the levels of both serum IL-8 and IL-12. Serum IL-8 level may be useful in determining metastatic breast cancer. Larger studies are needed to confirm this finding.

Is the thymidine labeling index a good prognostic marker in breast cancer?

BACKGROUND: The aim of the present study was to determine the prognostic relevance of thymidine labeling index (TLI) in patients with breast cancer. METHODS: TLI of the primary tumor was measured in 268 patients at the time of the surgical biopsy by an in vitro method. RESULTS: Fifty-four patients had stage I disease, and 138 patients had stage II disease, and 76 patients had stage III disease. One hundred-four patients were found to have low TLI-index (<3%), and 164 patients had high TLI-index (>/=3%). The median follow-up was 71.5 months (range, 6-138 months). The 5-year overall survival (OS) and disease free survival (DFS) rates was 84% and 74%, respectively. Lymph node involvement, tumor size more than 2 cm, high nuclear grade and estrogen receptor negativity were found to be associated with poorer DFS and OS rates. On subgroup analysis, however, the 5-year OS rate was significantly higher in the low TLI-group than in the high TLI-group in patients with stage I disease (100% vs 76%, p = 0.05). CONCLUSION: Our findings suggest that the prognostic significance of TLI appears to be limited to early breast cancer that might help to distinguish patients who need more aggressive adjuvant treatment.

Primary non-Hodgkin's lymphoma of the rectum.

BACKGROUND: Primary rectal lymphoma is a very uncommon disease, therefore, it has received little attention in the literature. Because of their rarity, rectal lymphomas are generally included in the group of large intestine lymphomas. CASE REPORT: We report here a case of primary rectal B-cell lymphoma in a 67-year-old woman. The tumor was originally located in the rectum without evidence of any other lymphoma-involved organ. Histological findings revealed diffuse large B-cell lymphoma. The clinical stage was IE according to the Ann Arbor system. International prognostic index (IPI) was I (low-intermediate risk). We preferred a non-surgical, organ-sparing treatment which started with chemotherapy followed by radiation. 12 months after the end of therapy, there is no sign of tumor recurrence in our patient. CONCLUSION: We suggest that histology-specific multidrug chemotherapy followed by radiotherapy seems to be a therapeutic approach that is appropriate fort this rare tumor.

Addition of topotecan to standard cisplatin/etoposide combination in patients with extended stage small cell lung carcinoma.

BACKGROUND: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell lung cancer (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC. MATERIALS AND METHODS: Twenty-one patients (median age 55 years, and 18 male) with chemotherapy-naive ED-SCLC were enrolled into the study. PET treatment consisted of etoposide 80mg/m(2), cisplatin 20mg/m(2) and topotecan 0.75mg/m(2) and all were given intravenously on days 1 to 3 for every 3 weeks. RESULTS: Leucopoenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Severe leucopenia/neutropenia were observed in 14 (67%)/12 (57%) patients, and only two (10%) developed febrile neutropenia. Severe thrombocytopenia was observed in 6 (29%) patients and one patient died due to orbital and cerebral haemorrhage. Dose reductions were required in 13 (62%) patients, delays in 8 (38%) patients and early treatment discontinuation in 3 (14%) patients. The overall response rate was 52.6% (95% CI: 28, 9-75.6) with 2 (10.5%) complete and 8 (42.1%) partial responses. The overall median survival time was 6.6 months (range 0.5-16.5 months) and the 6-month overall survival was 65.3%+/-11.7. The overall median survival time of responders was 9.7 months compared to 5.7 months in non-responders (p=0.026). CONCLUSION: Topotecan combined with PE regimen with this schedule and dosage does not seem to provide any benefit in terms of response and survival in ED-SCLC patients and does not deserve further studies.

Increased sister chromatid exchange frequency in young women with breast cancer and in their first-degree relatives.

The well-known increased risk of breast cancer (BC) in first-degree relatives of patients with BC has been related to shared genetic factors including defective DNA repair, with loss of genomic integrity. On the other hand, it can be hypothesized that early-onset breast cancer is also associated with overburden of heritable factors leading to increased DNA injury. In this respect, we analyzed sister chromatid exchange frequency (SCE) in 20 women with breast cancer (all < or =40 years old), in their first-degree female relatives, and in 20 age-matched healthy females without a personal or family history of cancer. SCE was significantly increased (P < 0.05) in patients (7.17 +/- 1.81 per metaphase) and in their first-degree relatives (6.44 +/- 0.98), compared with controls (5.85 +/- 0.72). There was no difference in SCE frequency between patients and their first-degree relatives. We suggest that the increased SCE in patients reflects a genomic instability that may be operative in carcinogenesis. Further, genomic instability is shared also by first-degree relatives, although none of them had a history of breast cancer at the time of the study.

Serum and urine survivin levels in breast cancer.

This study was conducted to investigate the serum and urine levels of survivin in patients with breast cancer and the relationships with known prognostic parameters and therapy. Forty-three patients with breast cancer and 21 healthy control subjects were investigated. Serum samples were obtained on the first admission before adjuvant and metastatic treatment were given and after two cycles of chemotherapy. Serum and urine survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA), respectively. There was no significant difference in the baseline serum and urine levels between patients with breast carcinoma and healthy controls (p = 0.19 and p = 0.84, respectively). None of the prognostic parameters analyzed were significantly correlated with the urine survivin concentrations. This was also true for serum survivin values, except for nodal involvement. Serum survivin levels were significantly higher in the patients with nodal involvement compared with node negatives (p = 0.043). However, serum survivin levels were not influenced by the number of involved nodes (p = 0.77). No significant correlation was found between the serum and urine levels of survivin (r = 0.15, p = 0.27). Serum and urine levels did not change significantly after chemotherapy (p = 0.59 and p = 0.50, respectively). In conclusion, the result of this study suggested that serum survivin level could be a sensitive marker for detecting metastases in lymph nodes from breast cancer patients. However, much research continues in this field, and exciting new knowledge will ultimately emerge.