Association between chemotherapy and disease-specific survival in women with borderline ovarian tumors: A SEER-based study.

BACKGROUND: The impact of chemotherapy on disease-specific survival in patients with borderline ovarian tumors (BOTs) has not been studied previously. METHODS: Patients with BOTs were identified from The Surveillance, Epidemiology, and End Results (SEER) database. Associations of chemotherapy and other risk factors with disease-specific survival were analyzed using Cox proportion hazards regression models. RESULTS: A total of 6065 patients diagnosed during 1988-2000 were selected. The mean age at diagnosis was 48.0 ±â€¯16.5 with a median follow-up time of 190.0 ±â€¯72.5 months. The majority of BOTs were at stage I (86.7%) and treated with surgery (99.3%). Chemotherapy and radiotherapy were given to 343 patients (5.7%) and 33 (0.5%) patients, respectively. A total of 296 patients (4.9%) died from this disease. Both univariate and multivariate survival analysis showed that chemotherapy, older age, bilateral tumor, advanced stage, non-surgery and radiotherapy were associated with worse disease-specific survival. The comprised effect of chemotherapy remained after patients were stratified by age, histology and stage. CONCLUSIONS: Chemotherapy is associated with worse disease-specific survival in patients with BOTs. Tumor laterality, age, stage and other treatments are also prognostic factors for this disease.

Incorporating PARP-inhibitors into clinical routine: A tailored treatment strategy to tackle ovarian cancer.

DNA repair mechanisms play a key role in oncogenesis and cancer progression in women with BRCA mutation-positive (BRCAm) ovarian cancer (OC). The BRCA1/2 and poly(ADP-ribose) polymerase (PARP) proteins are considered the foremost mediators among the various components of double-strand and single-strand repair, respectively. A series of new therapeutic drugs that target PARP have been developed for BRCAm OC. This class of agents provokes tumour-specific cytotoxicity with minimal side effects by inducing synthetic lethality, of which they are the first clinical example. The European Medicines Agency granted accelerated licensing approval for the first-in-class-drug that inhibits PARP, olaparib (Lynparza™, AstraZeneca). Olaparib can be used as a monotherapeutic maintenance treatment in patients with platinum-sensitive relapsed (germline and/or somatic) BRCAm high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer responsive to platinum-based chemotherapy. Seen in light of these recent events, this review article will focus on (a) how PARP-inhibitors exploit cancer-specific defects in the homologous recombination repair apparatus and (b) how BRCA testing is implemented in routine clinical care.

OK-432 injection therapy for cystadenocarcinoma of the parotid gland: A case report.

OK-432 is an immunomodulator that has been reported to be efficacious as an injection therapy for cervical lymphomas and ranulas. We performed OK-432 injection therapy to treat a cystadenocarcinoma of the parotid gland in a 72-year-old man. The 50 × 46-mm tumor was located in the deep lobe of the gland. The tumor had compressed the glossopharyngeal, vagus, and hypoglossal nerves, causing neurally mediated syncope, hoarseness, dysphagia, and dysarthria. A concentration of 5 KE/2 ml of OK-432 was injected. Within 2 months, the cyst had disappeared; no recurrence was apparent during 59 months of follow-up. To the best of our knowledge, no previous report has described injection of OK-432 for malignant cystic disease. We describe the injection method, injection dose, and postinjection course in the hope that this information will prove useful for future applications against malignant cystic disease.

MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1.

Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3'-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

Clinical characteristics of gynecologic cancer patients who respond to salvage treatment with Lingzhi.

Lingzhi or Ganoderma lucidum is a popular medicinal mushroom used as a health promotion herb in China and other Asian countries for thousands of years. There have many previous studies about the anti-cancer effects of lingzhi especially in vitro. The present study reports the clinical data of 5 gynecologic cancer patients who achieved stability in the disease after ingestion of lingzhi in the form of fruit body water extract and spores in a salvage setting. This report has been written to enhance the data describing the effect of lingzhi in cancer patients.

[Expression of COP9, JAK2, HSP and NADH in ovarian carcinoma tissues after taxol-chemotherapy and their significance].

OBJECTIVE: To study the expression of COP9, JAK2, HSP and NADH genes in ovarian carcinoma tissues after taxol-chemotherapy and their significance. METHODS: The up-regulated genes of JAK2, HSP, NADH and the down-regulated gene of COP9, which were revealed by micro-array from our previous study were examined by RT-PCR and real-time-PCR in 33 cases of ovarian cancer who previously received taxol-based chemotherapy (group 1), and 21 cases of ovarian cancer who never received chemotherapy before operation (group 2). RESULTS: The expression rate of COP9 gene in group 1 was detected markedly lower than that in group 2 (39% vs 95%, P < 0.01); whereas the expression rates of JAK2, HSP and NADH in group 1 were significantly higher that those in group 2 (91%, 97%, 94% vs 29%, 48%, 43%; all P < 0.05). And the expression of COP9, HSP and NADH genes had no significant differences among histological grades. However, a significantly higher expression of JAK2 gene was seen in grade 3 than in grade 1-2 (P < 0.01). No significant difference in the expression rates of the 4 genes was seen among various tumor types or chemotherapy courses (P > 0.05). Real-time PCR showed that the level of COP9 gene copies of group 1 was significantly lower than that of group 2 (568, 1866 respectively; P < 0.05). However, HSP, JAK2 and NADH genes had significantly higher copy numbers in group 1 than in group 2 (5766, 7653, 3200 in group 1 and 3341, 3094, 1522 in group 2, respectively; all P < 0.05). In the subgroup that received 6-10 chemotherapy courses, the copy concentrations of JAK2, HSP, NADH genes were higher than those in the subgroup that received 2-4 chemotherapy courses (all P < 0.05). In addition, we found a higher copy concentrations of JAK2, HSP, NADH genes in grade 3 than in grade 1-2 (all P < 0.05). Though no significant differences in gene copy concentrations of the 4 genes were seen among variable tumor types. In stage IV, the copy concentrations of HSP and NADH genes were higher than those in stage III (P < 0.01, P < 0.05 respectively), but the copy concentrations of COP9, JAK2 genes had no significant differences (both P > 0.05). There were positive correlations among JAK2, HSP and NADH genes (r = 0.56, 0.44, 0.57 respectively, all P < 0.01). COP9 gene was found to have a negative correlation with JAK2 gene (r = -0.48; P < 0.01), but not with HSP and NADH genes (r = -0.18, -0.06, respectively; both P > 0.05). CONCLUSION: The down-regulation of COP9 gene and up-regulation of JAK2, HSP, and NADH genes are related to the mechanism of drug-resistance in ovarian cancer.

Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer.

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of patients. These women require chemotherapy and surgery for optimal treatment. Conventional treatment is to perform surgery first and then give chemotherapy. However, it is important to determine whether there is any advantage to using chemotherapy prior to surgery. OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy prior to debulking surgery (neoadjuvant chemotherapy) compared with conventional treatment where chemotherapy follows maximal debulking surgery. SEARCH STRATEGY: RCTs were identified by searching The Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006), MEDLINE (Silver Platter, from 1966 to 1st Sept 2006), EMBASE via Ovid (from 1980 to 1st Sept 2006), CANCERLIT (from 1966 to 1st Sept 2006), PDQ (search for open and closed trials) and MetaRegister (most current search Sept 2006). SELECTION CRITERIA: Women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III-IV); randomized allocation to treatment groups which compared platinum-based chemotherapy before debulking surgery with platinum-based chemotherapy following debulking surgery. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent authors, and the quality of included trials was assessed by three independent authors. MAIN RESULTS: One RCT was identified as meeting the inclusion criteria. This trial randomized 85 women and compared standard debulking surgery followed by eight cycles of platinum-based chemotherapy with pre-operative intra-arterial platinum-based chemotherapy and ovarian artery embolization followed by debulking surgery and seven cycles of platinum-based chemotherapy. There was no statistical difference in median overall survival (OS) between the two treatment groups. Three on-going RCTs were identified and their results are awaited. AUTHORS' CONCLUSIONS: There is as yet no good evidence that neoadjuvant chemotherapy prior to debulking surgery for women with advanced epithelial ovarian cancer is superior to conventional debulking surgery and platinum-based chemotherapy.

[A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.

Initial chemotherapy followed by surgical cytoreduction for the treatment of stage III/IV epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to evaluate differences in morbidity, progression-free interval, and survival in women with advanced epithelial ovarian cancer treated with initial chemotherapy versus initial surgery. STUDY DESIGN: All women with epithelial ovarian cancer who were treated surgically at our hospital between January 1, 1995, and January 1, 2003, were eligible; the cases of 200 patients met the criteria and underwent retrospective chart review. RESULTS: Ninety-eight patients (49%) had initial chemotherapy, and 102 patients (51%) had initial surgery. Patients who received initial chemotherapy were more likely to have stage IV disease (initial chemotherapy, 27%, vs initial surgery, 8%; P = .042) and grade 3 disease (initial chemotherapy, 73%, vs initial surgery, 61%; P = .025). Optimal cytoreduction was achieved more often in patients who received initial chemotherapy (initial chemotherapy, 86%, vs initial surgery, 54%; P < .001). Only optimal cytoreduction (P = .022), and not treatment choice (P = .089), had an impact on median survival. CONCLUSION: Initial chemotherapy is a reasonable alternative to initial surgery for the treatment of selected patients with advanced epithelial ovarian cancer.

[Prognostic factors and better survival rate after the treatment of advanced ovarian cancer with neoadjuvant chemotherapy]. / Prognostichni faktori i podobrena prezhiviaemost ot prilaganeto na neadiuvantna khimioterapiia pri avansiral rak na iaichnika.

The better survival rate was evaluated as well as the prognostic factors due to the treatment with neoadjuvant chemotherapy for ovarian cancers FIGO Stage III and IV. For the period of 1990 till 2004 - 238 patients with histological diagnosis cystadenocarcinomas were evaluated. 192 patients received conventional chemotherapy after surgical treatment and 46 patients were treated with neoadjuvant chemotherapy after which a secondary cytoreductive surgery was used. The five years survival rate for the neoadjuvant chemotherapy was the same as the five years survival rate from the conventional chemotherapy. The patients with residual tumor < or = 2 cm. had a better prognosis than those with residual tumor more than 2 cm. There was a better prognosis for the patients treated with > or = 18 mg/m2/ week cisplatin from those treated with < 18 mg/m2/week.

Regional celiac artery infusion in the adjuvant treatment of pancreatic cancer.

UNLABELLED: We performed adjuvant celiac artery infusion in pancreatic cancer, to find out whether this treatment prolongs survival and changes the biology of the disease after resection, especially by reducing liver metastasis. PATIENTS AND METHODS: Thirty-one patients received cyclic celiac artery infusions (CAI) after resection of their pancreatic cancer (27 ductal, 4 cystadenocarcinoma). The treatment consisted of 6 cycles (1 cycle = 5 days treatment) intra-arterial infusion using Seldingers technique with mitoxantrone A (Novantron) 10 mg/m2 d1, 5-fluorouracil + folinic acid 600 mg/m2 + 170 mg/m2 d2-d4 and cis-platinum 60 mg/m2 d5. Four to 5-week intervals between each cycle of chemotherapy were scheduled. The patients were monitored for toxicity, development of disease progression and survival. RESULTS: The median survival time was 21 months. During an observation period of 19 months, 70% of the patients developed disease progression. In 50% of cases the progression was local, in 40% intraperitoneal while in 15% liver metastases developed. The median survival time of the CAI (celiac artery infusion)-treated patient group compared favorably to the median survival of 9.3 months in a matched historical control group, being significantly longer (p < 0.0003). CONCLUSION: Adjuvant celiac artery infusion seemed to prolong median survival and the occurrence of liver metastases appeared to be delayed or reduced.

Advanced ovarian carcinoma as a chronic disease: a case report and review.

Epithelial ovarian cancer is the fifth most common visceral malignancy in U.S. women, with the highest incidence in the sixth decade. There are often no early manifestations. Approximately 70% of patients present with advanced disease. Transvaginal ultrasonography is the single most useful test in the evaluation of a suspected pelvic mass. Treatment is based on the stage of the disease at presentation. Surgery is the mainstay of treatment. Chemotherapy is important in controlling residual disease following cytoreductive surgery and as neoadjuvant therapy in patients with advanced disease. The standard chemotherapy for advanced ovarian cancer is currently paclitaxel-carboplatin or paclitaxel-cisplatin. We present a patient who had an unusually prolonged survival after receiving ifosfamide-based combination chemotherapy. The data from the Sioux Valley Hospital USD Medical Center Cancer Registry also suggests that ifosfamide-based combination chemotherapy prolongs survival in patients with advanced ovarian cancer.

[Clinical characteristics of clear cell carcinoma of the ovary].

OBJECTIVE: To study the clinical characteristics of clear cell carcinoma of the ovary. METHODS: Forty three patients with clear cell carcinoma of the ovary and 51 patients with serous adenocarcinoma of the ovary who were admitted in Peking Union Medical College Hospital between 1984 to 2000 were analyzed retrospectively, and their chemosensitivities and the survival rates were compared. RESULTS: The percentage of early stage patients in the clear cell carcinoma of the ovary and the serous adenocarcinoma of the ovary was 14.4% and 3.8% respectively, the difference was significant (P < 0.005). In the late stage patients who underwent satisfactory cytoreductive surgery, the chemo-resistant rate (88.9%) in the clear cell carcinoma of the ovary was significantly higher than that (57.1%) of the serous adenocarcinoma of the ovary (P < 0.02), the 1-year survival rate (79.0%) in the clear cell carcinoma of the ovary was significantly lower than that (96.2%) of the serous adenocarcinoma of the ovary (P < 0.01). In the late stage patients who underwent unsatisfactory cytoreductive surgery, the chemo-resistant rate and the survival rate had no significant difference between the clear cell carcinoma of the ovary and the serous adenocarcinoma of the ovary (P > 0.05). CONCLUSIONS: There are more early stage patients with clear cell carcinoma of the ovary. We should conduct auxiliary therapy and close follow up to them after surgery. Clear cell carcinoma of the ovary is chemo-resistant to platinum-based chemotherapy and has poor prognosis.

Potential clinical utility of CA-125 in responsive but persistent large-volume ovarian cancer following platinum-based chemotherapy.

BACKGROUND: Despite the demonstrated clinical utility of the serum CA-125 antigen level in ovarian cancer, controversy exists regarding interpretation of "discordant" results between changes in this tumor marker and measurable disease masses. CASE: A patient with ovarian cancer cared for in the Gynecologic Cancer Program of the Cleveland Clinic Foundation receiving second-line single-agent carboplatin for recurrent disease demonstrated a major response in serum CA-125, but minimal shrinkage of a large painful abdominal mass. A laparotomy was performed both to define the nature of this mass and to attempt to relieve symptoms. The mass was found to be a large "inflamed pseudotumor with central necrosis." No viable tumors cells were found. CONCLUSION: This case represents an excellent example of the remarkably complex biology of malignant disease and suggests how evaluation of changes in CA-125 in women with ovarian cancer may be utilized in individual patients to develop optimal management plans.

Primary chemotherapy in stage IV ovarian cancer. A prospective phase II study.

BACKGROUND AND RATIONALE: Non-curative surgical cytoreduction of advanced tumors is associated with increased proliferation of the remaining tumor cells. Thus, appropriate preoperative chemotherapy should prevent both cell proliferation and the increase of resistant cells. The aim of the present study was to evaluate the efficacy and toxicity of primary chemotherapy (P-CT) in previously untreated patients with stage IV ovarian cancer (OC). PATIENTS AND METHODS: Thirty-four patients with stage IV OC were treated from January 1993 to April 2000 with P-CT. Eligibility criteria included: histologically or cytologically confirmed, unresectable stage IV OC and performance status < or = 3. P-CT consisted of four courses of carboplatin, cyclophosphamide and epirubicin until October 1996, and paclitaxel, carboplatin thereafter. Surgery followed P-CT. After the operation patients received two further courses of chemotherapy that were tailored according to their individual response. Median (M) age was 61 years, range 32-73; median performance status was 2. A total number of 197 courses of CT were administered, median 5.7 per patient. RESULTS: Complete or partial response (CR, PR) was observed in 28 patients (response rate 82%, 95% CI: 65.4% to 93.2%), disease stability and progression (SD, PD) was observed in three and three patients, respectively. Median time to progression was 16.45 months (range 4.8-90.4+), median survival time was 28 months (range 4.5 - 90.4+): 1-year survival rate was 94%. Toxicity according to WHO: nausea and vomiting grade (G) 2, 30% of patients; gastrointestinal G 2-3, 20% of patients; alopecia G 3, 88% of patients; hematological G 3-4, 73% of patients; neurologic G 2, 12% of patients. Nine pathological CRs were observed. CONCLUSION: Neoadjuvant treatment with CBDCA with either CTX and EPI or Taxol is feasible and shows activity in OC.

Sequence-dependent cytotoxicity of combination chemotherapy using paclitaxel, carboplatin and bleomycin in human lung and ovarian cancer.

Combination chemotherapy for non-small cell lung cancer (NSCLC) and ovarian cancer typically consists of a regimen of a taxane such as paclitaxel and a platinum-containing agent. Bleomycin, which halts cell cycle progression at G2 phase, is an agent which might thereby increase taxane cytotoxicity. The goal of this study was to evaluate the effect of different paclitaxel-platinum or paclitaxel-bleomycin schedules on cytotoxicity in human NSCLC and ovarian cancer cells. The simultaneous combination of paclitaxel and carboplatin exhibited simple additivity in vitro, while sequential exposure studies indicated that carboplatin followed by paclitaxel produced greater than additive cytotoxicity using the isobologram analysis of combinatorial effects. In contrast, the simultaneous combination of paclitaxel and bleomycin consistently exhibited greater than additive effects indicating a potentially synergistic combination. Sequential exposure studies of bleomycin followed by paclitaxel produced similar synergistic findings. Experiments in SCID mice evaluating the combinations of paclitaxel and bleomycin supported the in vitro results, as significantly enhanced A549 lung tumor growth inhibition was observed when paclitaxel was administered 1 h after bleomycin. The synergistic activity shown by the combination of bleomycin and paclitaxel indicates a potentially beneficial novel combination for treatment of NSCLC and ovarian cancer.

Bladder carcinoma associated with cyclophosphamide therapy for ovarian cancer occurring with a latency of 20 years.

BACKGROUND: Cyclophosphamide-induced urothelium cancer of the bladder is a well-known entity. The risk for inducing such cancer grows with duration and dosage of cyclophosphamide therapy. The lag time between termination of treatment and development of urothelial cancer has been observed to be between 9 months and 11 years. Single cases have been reported 14, 16, 17, and 21 years after cyclophosphamide treatment. CASE: We report a case of a bladder cancer occurring after a lag time of 20 years after oral therapy with cyclophosphamide for ovarian cancer. The bladder cancer was detected due to gross hematuria. CONCLUSION: It is of great importance for gynecologists to continue to care for patients who have received long-term cyclophosphamide treatment, even if the treatment was completed decades ago. One possible early symptom of cyclophosphamide-induced bladder cancer is painless hematuria. This can easily be used to detect bladder cancer in women at risk, even after a very long latency period.

Use of docetaxel (Taxotere) in patients with paclitaxel (Taxol) hypersensitivity.

Anaphylaxis or significant hypersensitivity reaction is one of the most catastrophic potential complications of chemotherapy. There is a 2-5% risk of hypersensitivity with paclitaxel, a commonly used chemotherapeutic agent for various cancers. Three patients, who developed hypersensitivity to paclitaxel infusion, received docetaxel without allergic reactions. Docetaxel may therefore be an alternative treatment for patients with paclitaxel hypersensitivity.