Management Of Advanced Ovarian Cancer Research Articles

Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a murine ovarian cancer model.

In photodynamic therapy (PDT), photosensitisers accumulate somewhat preferentially in malignant tissues; photoactivation with appropriate wavelength of light release toxic molecular species which lead to tumour tissue death. In order to target ovarian cancer with increased specificity, a chlorin-based photosensitiser (chlorin e6 monoethylendiamine monoamide) was conjugated to OC125, a monoclonal antibody recognising an antigen expressed in 80% of non-mucinous ovarian cancers. In previous work, this immunoconjugate (IC) was shown to be selectively phototoxic to cancer cells from ovarian cancer patients ex vivo and to localise preferentially in ovarian cancer tissue in vivo. In this study we report results from in vivo phototoxicology and photodynamic treatment studies using this IC in a murine model for ovarian cancer. A comparison of single vs multiple treatments was also made. For in vivo experimentation, Balb C nude mice were injected with 30 x 10(6) NIH:OVCAR 3 cancer cells to create an ascitic tumour model. Animals were then given intraperitoneal injections of the immunoconjugate (0.5 mg kg-1). Twenty-four hours later the intraperitoneal surfaces were exposed to 656 nm light from an argon-ion pumped-dye laser (50 mW, 656 nm), using a cylindrical diffusing tip fibre. The overall treatment was given either once or multiply. No animals died from treatment complications. Twenty-four hours following one and three PDT treatments, the percentage of viable tumour cells in the ascites of the treated animals analysed ex vivo was 34% and 5% of control for one and three treatments respectively. With respect to survival, all control mice (n = 18) died between 30 and 50 days. However, for those treated three times (n = 10), 40% were still alive after 50 days, and for those treated four times (n = 12) 58% were alive after 50 days. Evaluation with log-rank test revealed a significant survival with intraperitoneal PDT compared with controls (P = 0.0006). These preliminary results suggest that PDT with an OC125 immunoconjugate may be an effective therapy for the management of advanced ovarian cancer. Clinical application of this therapy needs to be further optimised and may require multiple treatments, similar to fractionated radiation therapy and cyclic chemotherapy, in order to control malignant disease with acceptable toxicity to normal tissue.

The role of high-dose chemotherapy in the management of advanced ovarian cancer.

Despite advances in terms of chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor. The issue of dose intensity remains controversial in treatment of patients with advanced ovarian cancer. This review focuses on the issues of dose intensity, particularly platinum dose intensity with regard to treatment of advanced ovarian cancer. Specific issues addressed include 1) results of the current generation of randomized trials of dose intensity in ovarian cancer; 2) the use of combination platinum strategies, focusing on attempts at paclitaxol dose intensification in the setting of advanced ovarian cancer; and 3) approaches utilizing high-dose chemotherapy both with bone marrow and progenitor self-support and the use of multiple cycle high-dose chemotherapy in patients with advanced disease.

The importance of dose and schedule in cancer chemotherapy: epithelial ovarian cancer.

Selection of specific appropriate drugs has been facilitated by a series of randomised clinical trials confirmed by overview analysis. Hitherto these issues have dominated the debate over optimal chemotherapy management of advanced ovarian cancer. The impact of true dose escalation therapy is yet to be evaluated but appears to be worthy of examination in demonstrably chemosensitive disease.

An overview of multi-variate analyses of prognostic variables with special reference to the role of cytoreductive surgery

Cytoreductive surgery is still widely believed to be a cornerstone in the management of advanced ovarian cancer. In the absence of data from prospective randomized trials, multi-variate analysis can assist in evaluating the role of optimal surgical cytoreduction relative to other possible prognostic variables. Published analyses of prognostic variables have been reviewed and the consistency and reproducibility of variables have been considered. When reviewing the most recent literature it is obvious that there is a need to develop a consensus as to the most important patient characteristics which should be reported. Furthermore, these characteristics need to be standardized as do definitions such as toxicity, grading, and response criteria and duration. Subjective variables such as performance status, histological grading and typing, present a special problem as these lack reproducibility. The overview of multi-variate analyses for prognostic variables such as residual tumour size, tumour size prior to cytoreductive surgery, cisplatin therapy, grade, stage, histology, and performance status demonstrates that the impact of individual prognosticators depends on the indicators included in the analysis and that the importance of these variables could change as new technologies and treatments are introduced. The collection of a single data base including all known variables reported for each patient with appropriate attention to the careful evaluation of subjective indicators should be undertaken, with a view to establishing a prognostic index. This would allow the relative risk for individual patients to be assessed.

The impact of subspecialty training on the management of advanced ovarian cancer

A retrospective study was conducted to determine the influence of subspecialty training in gynecologic oncology as well as several other covariates on the feasibility, operative mortality, and survival benefits of cytoreductive surgery for 263 patients with stages IIIC and IVA epithelial ovarian cancer. Covariates most predictive of an optimal (⩽ 1 cm) cytoreductive outcome were the diameter of the largest metastases before cytoreduction (⩽ 10 cm vs > 10 cm, P < 0.001) and the specialty training of the physicians present at surgery (gynecologic oncologists vs other, P < 0.001). Age influenced operative mortality most (<60 vs ⩾60, P < 0.001). Covariates found to most significantly influence survival time include the specialty training of the physicians present at surgery (gynecologic oncologists vs other, P < 0.0001), cytoreductive outcome (complete vs optimal, P = 0.001, optimal vs suboptimal, P < 0.0001), grade of tumor (grade 1 vs grades 2 and 3, P = 0.01), and pelvic disease status (frozen pelvis vs mobile primary tumor, P = 0.03). We conclude that patients with advanced epithelial ovarian cancer should undergo aggressive cytoreductive surgery by gynecologic oncologists, with the objective to remove all macroscopic disease. Subsequent treatment with platinum-based chemotherapy offers the best chance for long-term survival or cure.

A randomised study comparing standard dose carboplatin with chlorambucil and carboplatin in advanced ovarian cancer

A total of 161 previously untreated patients with FIGO stage III or IV epithelial ovarian cancer were randomised after surgery to receive six courses of either carboplatin 400 mg m-2 alone (Arm A) or carboplatin 300 mg m-2 with chlorambucil 10 mg day-1 for 7 days (Arm B). The median progression free survival (PFS) was similar: arm A: 45 weeks; arm B: 61 weeks (P = 0.830). Multivariate Cox regression analysis showed that the extent of residual disease and performance status were the most important prognostic factors for PFS. Fifty-two per cent of patients received dose escalations based on nadir blood counts, and 89% of all dose adjustments were made according to protocol. Failure to achieve a significant degree of leucopenia was associated with worse progression free survival (P less than 0.001). A total of 29.4% of patients fall into this category. The median survival was similar in both arms, i.e. 75 weeks. It is unlikely that there is any major clinical advantage to adding chlorambucil to single agent carboplatin for the management of advanced ovarian cancer, but whether used in combination or a single agent, the dose of carboplatin should be sufficient to cause at least grade I leucopenia. This may best be achieved by determining the initial dose based on renal function, and then adjusting subsequent doses according to nadir blood counts.

Tamoxifen in combination with cytotoxic chemotherapy in advanced epithelial ovarian cancer: A prospective randomized trial

One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate.

Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months.

Management of Advanced Ovarian Cancer

University Clinic of Obstetrics and Gynecology, Graz; and University Institute of Mathematics, Klagenfurt, Austria

Management of Advanced Ovarian Cancer

Since the end of 1979, extensive pelvic lymphadenectomy has been performed at the Graz University Clinic of Obstetrics and Gynecology in the operative treatment of ovarian cancer in stages IB to IV. In 27 of 48 patients (56.3 per cent) positive nodes were found. As shown in Table 1, positive nodes were found in all stages from stage IB onwards. The staging was done prior to lymphadenectomy; otherwise, all early stages with positive nodes would have to be included in stage III. Of special interest is the primary stage III in 36 cases thus comprising the most representative number. In this stage more than 60 per cent of positive nodes occurred. In 12 cases lymphadenectomy was done in second-look laparotomy. It became apparent that after operative and cytotoxic treatment with Adriamycin (Adria Laboratories, Inc., Dubin, OH), cisplatin, and cyclophosphamide pelvic lymph nodes were still found positive in 8 of 12 cases (66.7 per cent). In 16 cases apart from pelvic lymphadenectomy paraaor-tic nodes were also assessed. Enlarged nodes were extirpated when technically possible and when the patient's intraoperative condition would allow it. Thus, three cases were also recorded in which the nodes seemed positive but only by palpation. Even when including these cases the incidence of positive paraaortic nodes was clearly lower in all stages than that of pelvic nodes. Paraaortic nodes were positive only in cases of involved pelvic lymph nodes. When pelvic nodes were, negative, there were also no positive paraaortic nodes. The therapeutic value of pelvic lymphadenectomy must be evaluated critically as the number of cases is still rather small. In Table 2 two groups are compared. The first comprises cases after maximal debulking without lymphadenectomy but postoperative chemotherapy according to Parker and Lloyd. At the time of second-look laparotomy, 72.7 per cent of patients with a previously positive lymphadenectomy were tumor free; however, in those patients with negative lymph nodes, 100 percent showed no residual tumor (excepting one case of embryonic cancer) (Table 3). When considering the primarily excised nodes in 35 cases, only 22 out of 86 positive nodes or 26 per cent belonged to the common iliac group, 39 or 45 per cent to the external iliac nodes while 23 nodes or 27 per cent belonged to the interiliac group.

Management of Advanced Ovarian Cancer

Management of Advanced Ovarian Cancer

Intensive Surgical and Chemotherapeutic Management of Advanced Ovarian Cancer

We have presented the background and rationale for initiating a program of intensive surgical and chemotherapeutic management of advanced ovarian cancer. Our goal of excising all tumor masses larger than 1.5 cm in diameter has been explained and our operative approach described. The necessity for nutritional support has been emphasized. Preliminary results among patients with Stage III disease treated by optimal operation and Adriamycin-cyclophosphamide chemotherapy are encouraging. Aggressive operations have been unsuccessful when employed as secondary treatment. The single most important contraindication to extensive operation is the inability to initiate effective chemotherapy in the postoperative period.

Letter: Attitudes to abortion.

<h3>Objective</h3> Neoadjuvant chemotherapy followed by interval debulking surgery is an alternative for the management of advanced ovarian cancer (AOC). Owing to unresectable disease at initial evaluation, some patients received bevacizumab in addition to neoadjuvant chemotherapy. The aim of this study was to evaluate the safety and postoperative course of patients who had received bevacizumab before debulking surgery for AOC. <h3>Methods</h3> In 2012, we identified all patients with AOC who had received neoadjuvant bevacizumab before debulking surgery. We recorded patients’ characteristics, surgical course, and postoperative complications. <h3>Results</h3> Five patients were identified, of whom 80% were International Federation of Gynecology and Obstetrics stage 4 at diagnosis. All patients underwent surgery after 6 courses of neoadjuvant chemotherapy with carboplatin, paclitaxel, and bevacizumab. The median number of bevacizumab injections was 3 (3–4), and the median time between the last injection of bevacizumab and surgery was 54 days (34–110 days). One patient had a grade 3 complication (lymphocyst with puncture under computed tomographic scans). <h3>Conclusion</h3> In this preliminary study, debulking surgery after neoadjuvant chemotherapy that included bevacizumab did not increase the rate of postoperative complications when there was a reasonable interval between the last bevacizumab injection and surgery. Larger studies are warranted to assess surgical safety after antiangiogenic treatment in the neoadjuvant setting for advanced ovarian cancer.

Enzyme histochemistry of skeletal muscle. 3. Neurogenic muscular atrophies.

<h3>Objective</h3> The aim of this study was to explore the feasibility and safety of the laparoscopic approach after neoadjuvant chemotherapy among selected chemosensitive patients with advanced ovarian cancer. <h3>Methods</h3> The CILOVE study was a phase II prospective non-randomized multicenter study. It aimed to enroll 47 women with unresectable disease at the time of initial diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage IV and/or diffuse extensive carcinomatosis for advanced FIGO stage IIIC or patients unfit to withstand radical primary surgery), in response to chemotherapy and fit to undergo laparoscopy. <h3>Results</h3> Among the 48 patients enrolled in the trial, 44 (92%) patients underwent exploratory staging laparoscopy and, as a result, 41 patients were eligible for cytoreductive surgery. Among them, 32 were intended to be managed by laparoscopy and nine patients were managed by laparotomy. The conversion rate to laparotomy was 9.4% (3/32) and the reasons were multiple surgical adhesions (n=1), miliary carcinomatosis and adhesion to the intraperitoneal mesh (n=1), and poor laparoscopic evaluation of transverse colon involvement (n=1). All except one patient had optimal cytoreduction (97% complete cytoreduction, 3% incomplete cytoreduction (residual tumor &lt;2.5 mm)). The median operative time was 267 min (range 146–415) and the median estimated blood loss was 150 mL (range 0–500). Two patients had intra-operative complications: one diaphragm rupture that was repaired during laparoscopy and one bradycardia. Six patients experienced early post-operative complications (&lt;1 month), but there were no grade 3 and 4 complications (3 infections, 1 lymphoedema, 2 hemorrhage). After cytoreductive laparoscopy, the percentage of patients without progression at 12 months was 87.5%. <h3>Conclusions</h3> Interval ovarian cytoreduction by a laparoscopic approach is safe and feasible for patients with a favorable response to chemotherapy. With the widespread use of neoadjuvant chemotherapy in the management of advanced ovarian cancer, a minimally invasive approach may be a potential option.