Has serum CA 125 assay at the time of relapse a prognostic relevance for patients with recurrent ovarian carcinoma after primary cytoreduction and platinum- and paclitaxel-based chemotherapy?

PURPOSE OF INVESTIGATION: To correlate serum CA125 at relapse with survival in ovarian cancer patients who achieved a complete response after primary cytoreduction and paclitaxel- and platinum-based chemotherapy. MATERIALS AND METHODS: The study was conducted in 104 patients. RESULTS: The 25%, 50%, and 75% quantiles of CA125 levels at relapse were 46, 118, and 190 U/ml. By log-rank test, survival after recurrence was related to consolidation treatment (p = 0.046), platinum-free interval (PFI) (p < 0.000005), number of recurrence sites (p = 0.03), treatment at recurrence (p = 0.002), and serum CA125 taking 118 U/ml as cut-off (p = 0.013). On multivariate analysis, consolidation treatment (p = 0.007), PFI (p = 0.0001), treatment at recurrence (p = 0.01), and serum CA125 taking 118 U/ml as cut-off (p = 0.04) were independent prognostic variables for survival. CONCLUSIONS: Serum CA125 at relapse was an independent prognostic variable. Patients with serum CA125 > 118 U/m had 1.943 higher risk of death than those with lower antigen value.

Is there a role for postoperative treatment in patients with stage Ib2-IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study.

PURPOSE: Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. PATIENTS AND METHODS: This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p<0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p=0.0001). On multivariate analysis, consolidation therapy (p=0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p=0.0169) and consolidation therapy (p=0.0016) were independent prognostic variables for overall survival. CONCLUSION: Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment.

Adjuvant treatment and analysis of failures in patients with high-risk FIGO Stage Ib-II endometrial cancer: an Italian multicenter retrospective study (CTF study).

OBJECTIVES: The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion >50%, grade 2-3). METHODS: We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. RESULTS: Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p=0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). CONCLUSIONS: Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings.

Pathological response on surgical samples is an independent prognostic variable for patients with Stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: an Italian multicenter retrospective study (CTF Study).

OBJECTIVES: The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. METHODS: This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. CONCLUSIONS: Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome.

Characteristics and treatment of nonagenarian patients with vascular disease admitted to internal medicine services. NONAVASC-2 registry.

INTRODUCTION: Vascular disease (VD) is the most frequent cause of morbidity and mortality and its prevalence increases with age. Old patients are not included in studies on VD, their characteristics and treatments being unknown. OBJECTIVE: Know the clinical characteristics of nonagenarian patients hospitalized in Internal Medicine services with a diagnosis of established VD and the adequacy of their pharmacological management. MATERIAL AND METHODS: The NONAVASC-2 registry is an observational, prospective, multicentre study. Hospitalized patients for any cause were included. Data collection was carried out through an anonymous online database with sociodemographic, clinical, analytical, therapeutic and evolutionary parameters. RESULTS: One thousand forty-nine patients with a mean age of 93.14 years (57.8% women) were included. The prevalence of risk factors and VD was high: hypertension (84.9%), dyslipidemia (50.9%) and diabetes mellitus (29.4%). 33.4% presented severe-total dependency. 82.9% received antithrombotic treatment (53.7% antiplatelets, 25.4% anticoagulation and 3.8% double therapy). Only 38.2% received statins. The percentage of severe dependence (39.2% vs 24.1%; p = 0.00) and severe cognitive impairment (30.8% vs 13.8%; p = 0.00) was significantly higher among patients who did not receive them. 19% died during admission. CONCLUSIONS: Nonagenarian patients with VD present high comorbidity, dependence and mortality. Despite being in secondary prevention, 17% did not receive antithrombotics and only 38% received statins. The underprescription is conditioned, among other factors, by the functional status. More studies are necessary to determine the impact of this issue on their prognosis.

p53 nuclear accumulation in preneoplastic lesions and stage I uterine endometrioid adenocarcinoma.

A total of 118 endometrial neoplastic and preneoplastic lesions comprising 43 uterine endometrioid adenocarcinoma at stage I, 40 complex (adenomatous) hyperplasias and 35 atypical hyperplasias were examined for p53 nuclear accumulation to assess the incidence of p53 alterations in infiltrating carcinomas and to verify if p53 aberrations may allow the identification of a subset of premalignant cases with high risk of progression. No specific immunostaining was observed in the cases of complex hyperplasia without atypias. One (3%) of 35 atypical hyperplasias showed focal areas of p53 immuno-reactivity. The overall frequency of p53 overexpression in endometrial carcinomas was 54%. The distribution of cases with nuclear accumulation of p53 was significantly different (p=0.01) in tumours with different degree of invasiveness. In addition, p53 nuclear accumulation was observed more often in tumours with moderate (G2) or poor differentiation (G3) (p=0.03). Our data indicate that p53 aberrations are not early events in endometrial carcinogenesis and may be related with tumour progression and aggressiveness.

Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment of advanced cervical cancer.

The role of chemotherapy in the management of advanced cervical cancer has been long debated. Whereas some phase II trials have shown promising results with neoadjuvant chemotherapy followed by irradiation, most phase III trials failed to demonstrate any benefit with this sequential treatment in terms of loco-regional control and survival, mainly because chemotherapy could cause accelerated tumor clonogen resistant cell repopulation The data on cisplatin-based neoadjuvant chemotherapy before surgery appear to be more promising. This treatment modality can increase the operability rate and reduce the incidence of positive nodes and other pathological risk factors. However, very few randomized trials comparing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy versus conventional irradiation treatment are currently available, whilst data about long-term survival of chemo-surgical-treated patients are scanty. Recently five prospective randomized trials compared concurrent cisplatin-based chemotherapy and irradiation versus hydroxyurea plus irradiation or irradiation alone. All showed a significant improvement in the outcome of patients treated with concurrent cisplatin-based chemoradiation. Based on these data, the National Cancer Institute released a Clinical Announcement stating that concurrent cisplatin-based chemoradiation should be the new standard of therapy for high-risk early stage and locally advanced cervical cancer. The introduction of taxanes in both neoadjuvant chemotherapy followed by radical hysterectomy and concurrent chemoradiation could further improve the results of these two treatment modalities. A multicenter randomized trial comparing chemo-surgical treatment with concurrent chemoradiation is warranted to better define the optimum therapeutic strategy for patients with advanced cervical cancer.

Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management.

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.

Hormone replacement therapy and gynecological cancer.

The aim of this paper is to report the risk of development of gynecological cancer in women receiving hormone replacement therapy and to review the current knowledge on the administration of hormone replacement therapy following treatment of gynecological cancer. Estrogens alone may act as promoting factors for endometrial carcinogenesis. However, the addition of progestins reduces the risk of endometrial cancer to that of nonusers. Hormone replacement therapy could be given to selected patients following treatment for endometrial cancer. However, we think that this therapy should be reserved only for patients enrolled in controlled clinical trials. Ovarian cancer does not seem to be sensitive to estrogens, even if current literature does not allow firm conclusions to be drawn. Hormone replacement therapy should be offered to patients previously treated for ovarian cancer and cervical cancer.

An intensive follow-up does not change survival of patients with clinical stage I endometrial cancer.

BACKGROUND: The clinical benefit of an intensive follow-up protocol in endometrial cancer patients is still uncertain. MATERIALS AND METHODS: One hundred and thirty-three patients underwent initial abdominal surgery for clinical stage I endometrial cancer between January 1988 and December 1997 and were periodically followed-up until April 1999 or until death. After surgery, 89 patients received postoperative adjuvant treatment. Periodical surveillance included physical examination, vaginal smear and abdominal-pelvic ultrasound every 3-4 months for the first 2 years from surgery, every 6 months for the next 3 years and yearly thereafter. Chest X-ray was performed every 6 months for the first 2 years, every year for the next 3 years and with individually increasing intervals afterwards. An abdominal-pelvic CT scan was carried out yearly for 5 years. RESULTS: Twenty-four patients (18.0%) developed recurrent disease after a median time of 17.5 months (range, 6-64 months). Five-year actuarial disease-free survival was 81.2% in the whole series, and in detail 94.2% in the subset of patients with FIGO stage Ia grade 1 or 2 endometrioid adenocarcinoma, or stage Ib grade 1 endometrioid adenocarcinoma (low-risk), compared to 76.0 (p = 0.0472) in the subset of patients with stage Ia grade 3 endometrioid adenocarcinoma, stage Ib grade 2 or 3 endometrioid adenocarcinoma, stage equal to or greater than Ic endometrioid adenocarcinoma any grade, and aggressive histologies (high-risk). The site of recurrent disease was local in 6 (25.0%) patients, distant in 17 (70.8%), and local plus distant in 1 (4.2%). Eleven (45.8%) recurrences were symptomatic and 13 (54.2%) were asymptomatic. The median survival after recurrence was 10 months. Survival was longer in patients who relapsed after 17.5 months from initial surgery when compared to those who relapsed earlier (p = 0.02). Conversely, survival after recurrence was not related to patient characteristics at diagnosis, such as FIGO stage, tumor grade, myometrial invasion, histologic type, and lymph node status. It is noteworthy that survival was similar in asymptomatic women, in whom the relapse was occasionally detected by follow-up examinations, and in symptomatic ones. CONCLUSION: An intensive surveillance protocol seems to have no significant impact on the outcome of patients with clinical stage I endometrial cancer. Simplified follow-up programs tailored for patient subsets with different recurrence risk are required.

Platinum compounds and paclitaxel in advanced epithelial ovarian cancer.

Cisplatin is the most active agent currently employed in epithelial ovarian cancer. A meta-analysis of the Advanced Ovarian Cancer Trialists Group suggested that in terms of immediate survival platinum-based therapy was superior to nonplatinum regimens and that regimens including cisplatin were superior to single agent cisplatin given at the same doses. Intraperitoneal cisplatin seems to offer some clinical benefit when compared to systemic cisplatin in patients with minimal residual disease after initial surgery. An overview on the role of anthracyclines using data from the Advanced Ovarian Cancer Trialists Group and the Ovarian Cancer Meta-Analysis Project suggested that the addition of doxorubicin significantly improves survival and that the size of this benefit is of a similar magnitude to that of platinum. Carboplatin and cisplatin are equiactive, and the different spectrum of toxicities could offer an appropriate criterion for the choice of the platinum analogue to use in the individual patient. At present, there is no conclusive evidence that cisplatin dose intense regimens are beneficial, and the issue of dose intensity must still be considered experimental. The combination of cisplatin + paclitaxel is able to obtain a better progression-free survival and survival than the association cisplatin + cyclophosphamide. Phase I-II trials on regimens including platinum compounds, anthracyclines and paclitaxel are currently ongoing.

Serum anti-p53 antibodies in the follow-up of patients with advanced ovarian carcinoma.

Serum anti-p53 antibodies have been detected in different human malignancies, including ovarian carcinoma. In the present investigation these autoantibodies were retrospectively measured with a new ELISA (Immunotech, Marseilles, France) before first surgery and subsequently at different times during the course of disease from 40 patients with advanced ovarian carcinoma. Anti-p53 antibodies were preoperatively found in 15 (37.5%) patients. With regard to the follow-up of these 15 patients, anti-p53 antibodies were detected in 87.8% of the 41 samples drawn when there was clinical evidence of disease compared to 57.1% of the 14 samples collected when there was no clinical evidence of tumor (p = 0.037). As for the 25 patients whose serum originally scored negative, the autoantibodies were found only in 1.8% of the 113 samples obtained during the follow-up, independently of the status of disease. In conclusion, anti-p53 antibodies are often detected in serum from patients with advanced ovarian carcinoma. However, the serial measurement of these autoantibodies does not seem to give useful clinical information for the follow-up of these patients.

Surgical cytoreduction during second-look laparotomy in patients with advanced ovarian cancer.

BACKGROUND: The impact of surgical cytoreduction performed during second-look on the survival of patients with advanced ovarian cancer is still under debate. MATERIALS AND METHODS: The present retrospective investigation assessed 81 patients with advanced ovarian cancer who underwent second-look laparotomy after initial cytoreductive surgery and six cycles of platinum-based chemotherapy. RESULTS: At the beginning of the second-look, 31 patients were in pathological complete response, 7 had microscopic residual disease, 22 had macroscopic residual disease < 2 cm and 21 had a larger residuum. Twenty-two (51.2%) of the 43 patients with macroscopic disease underwent surgical cytoreduction during the second-look: 11 patients were completely cytoreduced, whereas 11 were debulked from residuum > 2 cm to macroscopic residuum < 2 cm. Patients with microscopic residual disease after the second-look had improved survival when compared to those with macroscopic residuum after re-exploration (median survival, 43 months versus 19.5 months, p = 0.002). Among the former, no difference in survival was detected between the patients who had microscopic disease at the beginning of the second-look and those who were surgically cytoreduced to microscopic disease. Moreover, the patients with macroscopic residuum < 2 cm after the second-look had a better survival than those with a larger residuum after re-exploration (median survival, 24 months versus 10 months, p = 0.0001). Among the former, no difference in survival was seen between the patients who had residual disease < 2 cm at the beginning of the second-look and those who were surgically cytoreduced to < 2 cm. However, ovarian cancer recurred in all the patients with small or large macroscopic residuum after the second-look. CONCLUSION: The complete resection of macroscopic persistent tumor seems to give ovarian cancer patients the highest likelihood of long-term survival and should represent the goal of surgical cytoreduction during second-look laparotomy.

Combination of cisplatin, epirubicin, and cyclophosphamide (PEC regimen) in advanced or recurrent endometrial cancer: a retrospective clinical study.

The combination of cisplatin (50 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (PEC regimen) was given every 4 weeks to 19 patients with advanced (n.2) or recurrent (n.17) endometrial cancer. The median number of cycles delivered to each patient was 5 (range, 2-8). All patients were evaluable for toxicity and 16 for response. Two (12.5%) patients experienced a complete response and 5 (31.2%) had a partial response, for an overall objective response rate of 43.7%. The median duration of objective response was 10 months (range, 3-28 months). Median survival was 10 months (range, 3-68+ months) in the whole series. According to response to chemotherapy, median survival was 12 months (range, 3-68+ months) for responders and 9 months (range, 6-17 months) for nonresponders. Hematologic toxicity was relatively frequent but it could be easily managed, and significant nonhematologic toxicities were not found except for nausea and vomiting. In conclusion, PEC regimen has a good activity in advanced or recurrent endometrial cancer, but the short duration of responses limits the impact of the treatment on survival time.

Preoperative serum E-cadherin assay in patients with ovarian carcinoma.

E-cadherin is a 120-kDa transmembrane glycoprotein involved in the calcium dependent adhesion of epithelial cells. Soluble E-cadherin fragment levels have been found to be significantly elevated in patients with different malignancies when compared to healthy controls (Katayama M. et al. Br. J. Cancer 69, 580-585, 1994). The aim of this paper was to assess the clinical relevance of preoperative serum E-cadherin assay in patients with ovarian carcinoma. E-cadherin was measured with a solid phase enzyme immunoassay based on a sandwich method using two mouse monoclonal anti-human E-cadherin antibodies. Preoperative serum E-cadherin levels were higher in 55 patients with ovarian carcinoma than in 31 patients with benign ovarian disease as controls, even though the difference did not reach the statistical significance (median value, range: 6615 ng/ml, 444-26,092 ng/ml versus 5531 ng/ml, 1548-12668 ng/ml, p = 0.063). However, the subset of the 36 patients with FIGO stage III-IV ovarian carcinoma had significantly higher antigen levels (median value, range: 7205 ng/ml, 444-26,092 ng/ml) when compared to controls (p = 0.039). Among patients with advanced ovarian carcinoma, preoperative serum E-cadherin correlated neither with the common clinico-pathological prognostic variables nor with the response to chemotherapy and survival. Our data seem to show that the preoperative serum E-cadherin assay does not offer useful clinical information for the management of patients with ovarian carcinoma.

Serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant v5 (sCD44-v5), and CD44 splice variant v6 (sCD44-v6) in patients with epithelial ovarian cancer.

Different variants of the cell adhesion molecule CD44 have been involved in malignant transformation and cancer metastasis. In the present investigation we assessed the preoperative serum levels of soluble CD44 standard (sCD44-st), sCD44 splice variant 5 (sCD44-v5), and sCD44 splice variant 6 (sCD44-v6) in 51 patients with ovarian cancer. Median preoperative sCD44-st, sCD44v5, and sCD44-v6 levels were 417 ng/ml (range, 240- > 602 ng/ml), 78 ng/ml (range, 5-314 ng/ml), and 86 ng/ml (range, 1-243 ng/ml), respectively. No significant relationship was detected between sCD44-st concentrations and the common clinicopathological variables. Conversely, sCD44-v5 and sCD44-v6 levels were significantly lower in FIGO stage III-IV than in stage I disease (p < 0.0001 and p = 0.001, respectively). Moreover, with regard to advanced ovarian cancer, sCD44-v5 levels were lower in patients with poorly differentiated (G3) than in those with moderately (G2) or well (G1) differentiated tumors (p = 0.038), as well as in patients whose residual disease was > 2 cm than in those with smaller residuum (p = 0.025). Similarly, sCD44-v6 levels were lower in patients with large residual disease (p = 0.05). The median value of serum sCD44-v6 was lower in patients with G3 than in those with G1-G2 tumor, but the difference was not significant. In conclusion, sCD44-st, sCD44-v5, and sCD44-v6 are detectable in sera from patients with epithelial ovarian cancer. A reduction in preoperative sCD44-v5 and sCD44-v6 levels seems to be associated with advanced, poorly differentiated tumors and with large residual disease after first surgery, and it might reflect an increased biological aggressiveness of the malignancy.

p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen.

BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway.

The serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) in patients with cervical cancer.

The pretreatment serum levels of soluble CD44 standard (sCD44st), CD44 splice variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) were retrospectively measured in 37 patients with untreated cervical cancer and in 36 patients with benign gynecological diseases as controls. Median sCD44-st levels were significantly higher in patients with cervical cancer than in controls (547 ng/ml, range 244-880 ng/ml versus 400.5 ng/ml, range 217-723 ng/ml, p = 0.004), whereas sCD44-v5 and sCD44-v6 concentrations were significantly lower in the former (34 ng/ml, range 0-140 ng/ml versus 44 ng/ml, range 11-109 ng/ml, p = 0.038; and 37 ng/ml, range 1-191 ng/ml versus 52.5 ng/ml, range 11-173 ng/ml, p = 0.007, respectively). sCD44-st, sCD44-v5, and sCD44-v6 levels were not related to FIGO stage and histologic type. Moreover, among patients with stage Ib-IIa cervical cancer, the preoperative levels of these glycoproteins correlated with neither the common prognostic variables nor the clinical outcome. Therefore, the serum assay of sCD44-st, sCD44-v5, and sCD44-v6 seems to have no clinical relevance for the management of patients with cervical cancer.

Molecular mechanisms of apoptosis and chemosensitivity to platinum and paclitaxel in ovarian cancer: biological data and clinical implications.

Apoptosis is a genetically regulated biological process that plays a major role in chemotherapy-induced tumor cell killing. It may be triggered by two major intracellular signaling cascades, the mitochondrial pathway and the death receptor pathway, both leading to caspase activation and cleavage of specific cellular substrates. The p53 gene is involved in the regulation of apoptosis. Caspase activation following wild-type p53 induction is associated with the release of the apoptogenic factors cytochrome c and Smac/DIABLO from the mitochondria, that is in turn controlled by the pro-apoptotic and anti-apoptotic Bcl-2 family proteins. In ovarian cancer p53 status is a strong predictor of response to platinum-based chemotherapy. Patients whose tumors have p53 mutations experience a lower chance of achieving a complete response following platinum-based regimens when compared to patients without p53 mutations. Conversely, experimental and clinical data seem to show that paclitaxel enhances apoptosis through a p53-independent pathway, that probably involves the Bax gene. Whereas patients with wild-type p53 tumors have a good chance to respond to platinum, patients with mutant p53 tumors may have a clinical benefit from the addition of paclitaxel to platinum-based chemotherapy. Therefore determining p53 status can be useful in predicting therapeutic response to specific drugs. Moreover the understanding of cellular mechanisms regulating apoptosis might offer a strong rationale for the combination of chemotherapy with other biological treatments.

Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?

PURPOSE OF INVESTIGATION: The aim of this retrospective study was to correlate some patient characteristics at relapse, including also baseline hemoglobin levels, with complete response rate and survival following second-line chemotherapy for recurrent platinum-pretreated ovarian carcinoma. METHODS: The investigation was conducted on 63 patients who received salvage chemotherapy with different agents for clinically detectable recurrent ovarian carcinoma following initial surgery and first-line platinum-based chemotherapy. Some patient characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin level, number of recurrence sites, ascites, platinum-free interval, and treatment-free interval) were related to complete response rate to salvage chemotherapy and survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range, 7.5-15.0 g/dl). RESULTS: Second-line chemotherapy obtained a complete response in 17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients, respectively. By univariate analysis, complete response rate was related to baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and treatment-free interval (p = 0.0048). Multiple logistic regression showed that platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were independent predictors of complete response. Patients with baseline hemoglobin levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when compared to those with lower hemoglobin values. The platinum-free interval was the only independent prognostic variable for survival after recurrence (p = 0.0141), whereas baseline hemoglobin level was not related to survival at univariate nor at multivariate analysis. CONCLUSIONS: Baseline hemoglobin level is an independent predictor of complete response to salvage chemotherapy in patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be paid to anemia correction in these patients, with the aim of improving both the chance of response to salvage treatment and the quality of life.