A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer

Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free survival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The purpose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an IP cisplatin regimen to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.     

Meta-analysis of cisplatin, doxorubicin, and cyclophosphamide versus cisplatin and cyclophosphamide chemotherapy of ovarian carcinoma.

OBJECTIVE: To compare the survival with cisplatin, doxorubicin (Adriamycin), and cyclophosphamide versus that of cisplatin and cyclophosphamide in women with advanced epithelial ovarian cancer, to evaluate the effect of dose intensity, and to evaluate meta-analysis methodology. METHODS: Meta-analysis was done on 30 studies of 2060 women with stages III and IV epithelial ovarian cancer. All had 3-year survival data, adequate follow-up, no other chemotherapy, no radiation therapy, and had information for various prognostic variables (age, stage, grade, and residual disease). We used four different methods of meta-analysis: pooled published data and modified effect-size analyses of the entire group (30 studies), and pooled published data and effect-size analyses of the subset of five prospective randomized studies. RESULTS: Three-year survival for the entire group was 43% for cisplatin, doxorubicin, and cyclophosphamide versus 36% for cisplatin and cyclophosphamide; for the five prospective randomized studies, the rates were 46 and 35%, respectively. The survival advantage of cisplatin, doxorubicin, and cyclophosphamide was statistically significant when analyzed by the pooled published data and modified effect-size meta-analysis of the entire group and the pooled published data meta-analysis of the five prospective randomized studies. The effect-size meta-analysis of the five prospective studies did not reach statistical significance. Total dose intensity and doxorubicin dose intensity were not significantly associated with survival advantage in cisplatin, doxorubicin, and cyclophosphamide use. CONCLUSIONS: There seems to be a survival advantage to treatment with cisplatin, doxorubicin, and cyclophosphamide versus treatment with cisplatin and cyclophosphamide. We believe this to be due to the properties of multiagent chemotherapy (the addition of doxorubicin) rather than to increased dose intensity. In addition, we believe that physicians need to familiarize themselves with meta-analysis methodology.     

Systematic review of systemic therapy for advanced or recurrent endometrial cancer

OBJECTIVE: To evaluate the chemotherapeutic options for women with advanced or recurrent endometrial cancer. METHODS: The MEDLINE, CANCERLIT and the Cochrane Library databases were searched from 1984 to March 2005 for randomized controlled trials (RCTs) comparing chemotherapy regimens in patients with advanced or recurrent endometrial cancer. Studies were included only if patients had measurable or evaluable disease, and/or response rates were reported. RESULTS: Seventeen RCTs compared regimens involving chemotherapy and/or hormonal therapies. Three chemotherapy trials demonstrated a statistically significant difference in response rates between treatment arms, but only one of these trials showed a modest survival advantage. The addition of cisplatin to doxorubicin in two RCTs significantly improved response rates (1.7- to 2.5-fold higher) but did not impact on survival. In two other RCTs using cisplatin and doxorubicin as standard therapy, the addition of paclitaxel improved response rates (57% versus 34%) and median survival (15.3 versus 12.3 months) when combined with cisplatin and doxorubicin but not when combined with doxorubicin only. Toxicity was increased with the three-drug combination. Quality of life was assessed in one trial, which is currently only in abstract form. Medroxyprogesterone acetate (200 mg/day) was effective in one RCT, particularly in patients with well-differentiated, receptor-positive tumors. CONCLUSIONS: Combination chemotherapy with doxorubicin and cisplatin results in higher response rates than doxorubicin alone. The addition of paclitaxel to either of these regimens resulted in a small survival advantage in one trial using all three drugs. In light of the limited survival advantage associated with this regimen, the use of less toxic combinations of taxanes with carboplatin requires further study. Medroxyprogesterone acetate is useful in selected patients.     

Clinical implication of medroxyprogesterone acetate against advanced ovarian carcinoma: a pilot study

PURPOSE OF INVESTIGATION: The present study was performed to identify the effects of medroxyprogesterone acetate (MPA) plus adjuvant chemotherapy on advanced epithelial ovarian carcinoma (FIGO Stage III/IV). METHODS: A total of 50 patients were enrolled in this study. A relatively low dose of MPA (200 mg/day) after surgery was administered in combination with platinum-based chemotherapy and the treatment was continued for two years. Patients' backgrounds were also analyzed. RESULTS: Relapse-free survival (p < 0.05) and overall survival (p < 0.001) rates in FIGO Stage III/IV ovarian cancer patients with MPA combined chemotherapy were significantly longer than the control group. The effect was more prominent in the higher progesterone receptor expression group. The chemotherapy regimens (cyclophosphamide, doxorubicin and cisplatin vs paraplatin plus cyclophosphamide or paclitaxel) did not affect prognosis. CONCLUSION: MPA with platinum-based chemotherapy as an adjuvant therapy might improve the prognosis in FIGO Stage III/IV epithelial ovarian cancer cases. A randomized controlled study is still needed for further analyses.     

Chemotherapy for recurrent epithelial ovarian cancer previously treated with platinum--a systematic review of the evidence from randomized trials

PURPOSE: To evaluate the chemotherapeutic options for women with recurrent epithelial ovarian cancer who have received platinum-based chemotherapy. METHODS: A systematic search of the Medline, CancerLit and Cochrane Library databases was performed for the period from 1984 to June 2001 to find randomized trials comparing second- or higher-line chemotherapy regimens in patients with recurrent platinum-pretreated epithelial ovarian cancer. RESULTS: Seven randomized trials have failed to demonstrate the clear superiority of any one chemotherapy regimen in terms of improvements in long-term survival, quality of life or response rate. One trial detected a statistically significant difference between treatments in progression-free survival, which was longer with cyclophosphamide/doxorubicin/cisplatin than with paclitaxel in women with platinum-sensitive ovarian cancer. Another trial did not show a difference between liposomal doxorubicin and topotecan overall in women with recurrent ovarian cancer but a subgroup analysis detected a significant survival advantage for liposomal doxorubicin over topotecan in women with platinum-sensitive disease. CONCLUSION: The evidence available does not support firm conclusions about the preferred chemotherapy regimen for recurrent ovarian cancer. Randomized trials that compare new drugs with current standard treatments are needed.     

A phase II double-blind randomized study of the simultaneous administration of recombinant human interleukin-6 and recombinant human granulocyte colony-stimulating factor following paclitaxel and carboplatin chemotherapy in patients with advanced epithelial ovarian cancer

PURPOSE: Recombinant human interleukin-6 (rhuIL-6) is a glycosylated cytokine with hematopoietic stimulatory effects. In particular, preclinical studies suggest the agent can stimulate thrombopoiesis, even in conjunction with chemotherapy. We attempted to determine whether higher dose chemotherapy for ovarian cancer was possible given the pharmacologic use of this important growth factor. METHODS: We conducted a randomized, double-blind phase II study of IL-6 plus granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF in combination with a standard chemotherapy regimen. Patients with epithelial ovarian cancer, stages Ic to IV, were eligible. All patients were previously untreated with chemotherapy and had Karnofsky performance status >/=60. rhuIL-6 (Escherichia coli, SDZ ILS 969) 1.0 micrograms/kg or placebo was given subcutaneously on days 2-8 every cycle together with G-CSF 5.0 micrograms/kg subcutaneously days 2-15, following administration of paclitaxel 175 mg/m2 as a 3-h infusion and carboplatin given to a desired AUC of 7.5 on day 1 every 21 days. RESULTS: Fifty patients were entered in this study, although the study was temporarily suspended by the FDA in midstudy over manufacturing concerns. Therefore, 37 patients were evaluable for efficacy of growth factor; 19 patients received placebo plus G-CSF and 18 rhIL-6 plus G-CSF. There was no difference in prognostic variables between these two groups. Platelet nadirs were lower in the first cycle for the placebo group (P = 0.004, Wilcoxon sum-rank test) but not in other cycles. There was no statistically significant difference in cycle treatment delays, carboplatin dose delivered, number of patients with grade 4 thrombocytopenia, or platelet transfusion. Nonetheless, the trend of the data favored IL-6 in all cases. CONCLUSIONS: This study demonstrated a minimal effect (statistically significant in the first cycle only) on thrombopoiesis in women undergoing paclitaxel and carboplatin therapy of ovarian cancer. No clinically significant effect on actual chemotherapy delivery was demonstrated, however. Future studies, if warranted, to ameliorate thrombocytopenia should be carried out with regimens producing even greater thrombocytopenia than the current regimen in the control arm.     

Medikamentöse Primärtherapie beim fortgeschrittenen epithelialen Ovarialkarzinom

Standard therapy of advanced primary ovarian cancer consists of maximum debulking surgery followed by polychemotherapy. According to metaanalyses, platinum containing chemotherapy leads to higher response rates and longer survival than other regimens. Adding paclitaxel to cisplatin increases survival by one year as shown by the GOG-111-Study and confirmed by a European-Canadian intergroup study recently. The German AGO-study group demonstrated that replacing cisplatin by carboplatin in combination with paclitaxel leads to similar response and survival rates but lower toxicity.However, in spite of these advances prognosis of advanced ovarian cancer remains poor and most patients still relapse and die within less than 5 years after diagnosis. New therapeutic regimens such as additional anthracyclines or sequential cytotoxic therapies are currently investigated in randomized studies by the AGO.     

What is the role of dose-dense therapy?

Abstract.   van der Burg MEL, van der Gaast A, Vergote I, Burger CW, van Doorn HC, de Wit R, Stoter G, Verweij J. What is the role of dose-dense therapy? Int J Gynecol Cancer 2005; 15(Suppl. 3): 233–240.
The introduction of paclitaxel/platinum combination chemotherapy and (interval) debulking surgery has significantly improved the prognosis of patients with ovarian cancer. Yet, many patients die of drug-resistant disease. Second-line chemotherapy may result in prolonged secondary remissions with alleviation of symptoms and improvement of quality of life. The response to second-line chemotherapy is strongly related to platinum sensitivity. More than 60% of platinum-sensitive patients respond to a re-challenge with platinum-containing chemotherapy. In platinum-resistant patients, on the contrary, the response rate to a re-challenge with 3-weekly platinum or any nonplatinum chemotherapy is less than 20%. The response to dose-dense weekly platinum-based regimens ranged from 48% to 64% in platinum-resistant patients. Moreover, the majority of the patients responded within 8 weeks after the start of the treatment. The progression-free survival ranged from a median of 5 months in a study using cisplatin/etoposide, to 11 months in a study with paclitaxel/carboplatin. The median survival was 11–15 months. The outpatient weekly paclitaxel/carboplatin regimen, with paclitaxel at a dose of 90 mg/m² and carboplatin at area under the curve 4, seems similarly effective and is better tolerated. Dose-dense weekly paclitaxel/carboplatin is an effective and well-tolerated therapy for platinum-sensitive, as well as platinum-resistant tumors. Responses to therapy are observed within 8 weeks in the majority of the patients. Whether a weekly regimen indeed is more effective than 3-weekly paclitaxel/carboplatin needs to be answered in a randomized study.     

Future Strategies for the Treatment of Advanced Epithelial Ovarian Cancer Using High-Dose Chemotherapy and Autologous Bone Marrow Support

The response and long-term disease-free survival rates with standard-dose salvage chemotherapy for advanced ovarian cancer are commonly reported to be less than 20 and 10%, respectively. More than 200 women with advanced, refractory, ovarian cancer have received high-dose chemotherapy regimens with autologous bone marrow support (ABMS) for their disease. A feature of the vast majority of the studies is the strikingly high response rates of 70-82% achieved when marrow-supported intensive therapy is administered to women with refractory ovarian cancer. Applying such high-dose therapy earlier in the disease course when the tumors are less resistant will likely produce durable antitumor effects. To further evaluate the effectiveness of high-dose therapy, the Southwest Oncology Group (SWOG) has initiated a phase II study for stage III/IV ovarian cancer with residual disease (microscopic up to 3 cm) following one cisplatin- or carboplatin-based induction regimen (SWOG 9106). Patients will be randomized to receive one of two high-dose regimens with ABMS: cyclophosphamide, cisplatin, and thiotepa or cyclophosphamide, carboplatin, and mitoxantrone. This initial trial is a feasibility study to evaluate whether such high-dose regimens can be given in a cooperative group setting to the ovarian cancer patient population. If the trial is successfully completed, one of the two regimens will be chosen (based on lesser toxicity) to use in a phase III randomized trial of high-dose therapy and ABMS versus standard therapy for high-risk ovarian cancer patients.     

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel,followed by maintenance paclitaxel therapy in stage IV ovarian,fallopian tube,and peritoneal cancers: a Southwest Oncology Group trial

OBJECTIVE: To improve the survival of women with stage IV epithelial ovarian cancer the Southwest Oncology Group conducted a phase II trial examining two novel treatment strategies: (a) modification of the chemotherapy regimen (carboplatin/paclitaxel) based on evidence of response during treatment and (b) "maintenance therapy," with the monthly administration of single agent paclitaxel (maximum 2 years). METHODS: Individuals with histologically documented stage IV ovarian, fallopian tube, or peritoneal cancers initially received a maximum of 3 courses of single agent carboplatin (AUC 6), with the decision to administer a subsequent course based on specific response criteria (i.e., declines in serum CA-125 or shrinkage of measurable mass lesions). This was followed by single agent paclitaxel (150 mg/m(2)), delivered every 2 weeks for a maximum of 6 courses, again based on evidence of continued response to the treatment program. Finally, in the absence of disease progression or unacceptable toxicity, patients received single agent paclitaxel (175 mg/m2) for a maximum of 24 monthly courses. The primary study end point was 2-year overall survival, which was to be compared to the survival of a previously published historical control population [stage IV ovarian cancer patients treated with a "standard" cisplatin/paclitaxel regimen (GOG 111; McGuire WP, N Eng E J Med 1996; 334:1)]. This analysis was employed to determine if this novel strategy was worthy of further clinical investigation in a controlled clinical trial. RESULTS: There were 53 patients entered this multicenter study, of whom 50 were evaluable for toxicity and 51 for survival. There were 2 treatment-related deaths. Grades 2 and 3 neutrotoxicity were observed in 18 and 4% of patients, respectively. There were no major treatment-related protocol violations. The overall 2-year survival was 48% (95% CI, 34-62%), compared to 60% for the historical control group. CONCLUSIONS: While this trial demonstrated the feasibility of delivering a treatment regimen requiring frequent alternations in therapy based on predetermined changes in objective parameters of response, further exploration of this specific management approach does not appear warranted in stage IV ovarian cancer, based on the survival outcome compared to a reasonably similar historical control population. As this trial demonstrates, the prospective determination of clinical end points in a phase II study (e.g., 2-year survival) that will lead to continued evaluation of a particular investigative strategy in a large-scale randomized trial can be an effective method to reduce the bias and uncertainty often associated with this complex decision process.     

紫杉醇化疗在宫颈癌中的临床应用

紫杉醇为广谱有效的抗实体瘤药物,用于宫颈癌患者治疗已进行广泛临床研究,证实其可靠有效。从单药、双药及三药化疗等方面,综述近年紫杉醇治疗宫颈癌的临床应用。紫杉醇（T）联合顺铂（P）或卡铂（C）化疗方案优于紫杉醇单药或三药化疗,安全有效。尤其在新辅助化疗中;与顺铂相比,卡铂肾毒性小,无需水化,TC方案相对简单;TP或TC配合放疗疗效显著;紫杉醇周疗与3周疗法比较疗效类似,不良反应较小。     

Pharmacokinetic analysis of paclitaxel and carboplatin in a patient with advanced ovarian cancer during hemodialysis--case report

We examined pharmacokinetics of paclitaxel and carboplatin in a FIGO Stage IIIb ovarian cancer patient with hemodialysis-dependent chronic renal failure. The patient suffered from recurrence of the disease after treatment with optimal debulking surgery and postoperative chemotherapy consisting of cisplatin, epirubicin and cyclophosphamide, and she was treated with combined paclitaxel and carboplatin as second-line chemotherapy. The carboplatin dose was chosen to produce a target area under the concentration/time curve (AUC) of 5.0 microg-min/ml according to a published formula. Four-hour hemodialysis was started 24 hours and 16 hours after the end of carboplatin administration in the first and second courses of the chemotherapy, respectively. Pharmacokinetic studies showed that the AUCs of free platinum were 8.03 and 5.69 microg-min/ml in the first and second courses of the chemotherapy, respectively, suggesting that the AUC of carboplatin is affected by hemodialysis. However, an attenuation pattern of paclitaxel was almost similar between the first and the second courses, indicating that the change in blood concentration of paclitaxel was similar to that of patients with normal renal function. Hematological and nonhematological adverse effects were at an acceptable degree. The evidence suggests that even patients with chronic renal failure can undergo combination chemotherapy of paclitaxel and carboplatin without suffering any severe adverse effects by determining the time to start hemodialysis.     

Devastating effects of chemotherapy: deafness and acute renal failure in a patient with epithelial ovarian cancer

Abstract.   Ozguroglu M, Sari O, Turna H. Devastating effects of chemotherapy: deafness and acute renal failure in a patient with epithelial ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 394–396.
Paclitaxel and platinum combination is the standard chemotherapy regimen for patients with advanced epithelial ovarian cancer. The dose-limiting toxicity effects of this combination are myelosuppression and neuropathy. Herein, we report a case of a 71-year-old female with advanced epithelial ovarian cancer who developed bilateral total loss of hearing and acute renal failure related with paclitaxel- and carboplatin-based chemotherapy. Acute renal failure accompanied by complete loss of hearing in patients treated with carboplatin and paclitaxel combination has not been previously reported. This uncommon adverse effect of carboplatin and paclitaxel combination was discussed, and all the literature in English related with the toxicity of paclitaxel and carboplatin were reviewed.     

A case of prolonged carboplatin therapy in a patient with carboplatin hypersensitivity

OBJECTIVES: Platinum-containing chemotherapeutic drugs have high response rates yet are known to cause hypersensitivity reactions. Attempts have been made to rechallenge allergic patients with prolonged desensitization infusion regimens. CASE: A female with advanced peritoneal cancer went into remission after six cycles of paclitaxel/cisplatin. Her cancer recurred 17 months later and she was treated with paclitaxel/carboplatin. A hypersensitivity reaction to carboplatin occurred during the fourth cycle and further carboplatin was withheld. With the second recurrence carboplatin was resumed using a prolonged desensitization regimen. The patient had a third recurrence and has recently completed cycle 15 of carboplatin for a total of 56 cycles. CONCLUSIONS: A carboplatin desensitization regimen may allow patients with platinum-sensitive ovarian or peritoneal cancer to continue to benefit from its efficacy.     

Paclitaxel/carboplatin versus cyclophosphamide/adriamycin/cisplatin as postoperative adjuvant chemotherapy for advanced endometrial adenocarcinoma

AIM: There is no standard chemotherapy regimen for patients with advanced endometrial adenocarcinoma. In our hospital, a cyclophosphamide/adriamycin/cisplatin (CAP) regimen was commonly used as adjuvant chemotherapy. However, since October 1999 a paclitaxel/carboplatin regimen has been substituted for CAP. To evaluate the antitumor activity and toxic effects of those regimens, we retrospectively reviewed cases that were treated in our hospital. METHODS: Twenty-eight patients who underwent surgery and had histologically confirmed advanced endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics stage III/IV, received combination chemotherapy. Treatment consisted of cisplatin, adriamycin and cyclophosphamide (CAP group, n = 16), or paclitaxel and carboplatin (paclitaxel/carboplatin group, n = 12). The response rate (RR), progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. RESULTS: In the CAP group, complete response (CR) was observed in six patients and partial response (PR) in three, for an RR of 64.3%. In the paclitaxel/carboplatin group, CR was observed in five and PR in two, for an RR of 77.8%. The 3-year PFS and OS rates were 50.0% and 75.0% in the paclitaxel/carboplatin group, and 37.5% and 50.0% in the CAP group, respectively, and there was no significant difference between the two groups. National Cancer Institute Common Toxicity Criteria grade 3-4 thrombocytopenia and gastrointestinal toxicities occurred significantly less frequently in the paclitaxel/carboplatin group (0% and 16.7%) than in the CAP group (31.3% and 68.8%) (P = 0.0389 and P = 0.0062). CONCLUSIONS: We conclude that paclitaxel/carboplatin is a promising regimen which could be substituted for CAP, with major activity and a highly acceptable toxicity profile for the treatment of advanced endometrial adenocarcinomas.     

紫杉醇化疗在宫颈癌中的临床应用

紫杉醇为广谱有效的抗实体瘤药物,用于宫颈癌患者治疗已进行广泛临床研究,证实其可靠有效。从单药、双药及三药化疗等方面,综述近年紫杉醇治疗宫颈癌的临床应用。紫杉醇（T）联合顺铂（P）或卡铂（C）化疗方案优于紫杉醇单药或三药化疗,安全有效。尤其在新辅助化疗中;与顺铂相比,卡铂肾毒性小,无需水化,TC方案相对简单;TP或TC配合放疗疗效显著;紫杉醇周疗与3周疗法比较疗效类似,不良反应较小。     

初诊上皮性卵巢癌的一线化疗

晚期上皮性卵巢癌的初始治疗模式为肿瘤细胞减灭术+铂类为基础的联合化疗+一线维持治疗。文章主要阐述了初诊上皮性卵巢癌一线化疗方案的演变和规范应用。紫杉醇联合卡铂3周疗方案仍然是初治上皮性卵巢癌的一线首选化疗方案,其卓越地位无法撼动。同时,文章还回顾了初始化疗中使用贝伐珠单抗的指征,以及其他一线化疗方案的选择指征。最后,文章指出了临床实践中上皮性卵巢癌化疗不规范的问题,强调应重视化疗的规范性,以助于提高我国晚期上皮性卵巢癌患者的生存率。     

Interferon-gamma in combination with carboplatin and paclitaxel as a safe and effective first-line treatment option for advanced ovarian cancer: results of a phase I/II study

We have previously shown that interferon-gamma 1b (IFN-gamma) in combination with cyclophosphamide and cisplatin significantly prolongs progression-free survival in ovarian cancer. In this phase I/II study, we examined if administration of IFN-gamma is also safe in combination with the current standard treatment, paclitaxel and carboplatin. Thirty-four patients with newly diagnosed advanced epithelial ovarian cancer, FIGO stage III/IV, were treated for six to nine cycles with paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] 5) every 3 weeks. IFN-gamma was administered in an escalating dose from 6 days/cycle with 0.025 mg sc up to 9 days/cycle with 0.1 mg sc. As expected, administration of IFN-gamma was associated with flu-like symptoms. Grade 3/4 neutropenia was observed in 74% (25 out of 34) of patients. Other side effects, in particular peripheral neuropathies, were within the previously observed ranges for the paclitaxel plus carboplatin combination. Overall response rate (complete or partial response) in patients who received either six or nine doses (0.1 mg) of IFN-gamma/cycle (n = 28) was 71%. IFN-gamma is safe in combination with carboplatin and paclitaxel for first-line treatment of patients with advanced ovarian cancer. This combination should be further evaluated as an immunotherapeutic treatment option for ovarian cancer.     

Pharma Update Genitalkarzinome

Ovarian cancer

In early stage ovarian cancer chemotherapy containing platinum is recommended. In an advanced or recurrent situation combined chemotherapy with carboplatin/paclitaxel (area under the curve AUC5 175 mg/m²) is indicated. The vascular endothelial growth factor (VEGF) targeting agent bevacizumab can prolong the progress-free interval. For the treatment of platinum-sensitive ovarian cancer the preferred agents are carboplatin/gemcitabine, carboplatin/paclitaxel and carboplatin/caelyx. Platinum-resistant recrudescence primarily indicates a monochemotherapy and the recommended therapeutic options are polyethylene glycol (PEG) liposomal doxorubicin/topotecan/gemcitabine/paclitaxel.

Cervical cancer

A combined radiochemotherapy containing cisplatin is considered to be the standard of care in neoadjuvant and adjuvant treatment as well as in recurrent situations. Neoadjuvant dose-dense chemotherapy improves the 5-year survival rate and reduces overall mortality. Adjuvant chemotherapy only is not indicated. In a recurrent or metastasized situation for radiation-naive patients radiochemotherapy is indicated. The only approved regimen in Germany is a combination of cisplatin and topotecan. Results of the GOG 240 trial confirmed an enhancement of the progress-free survival with addition of the antibody bevacizumab.

Endometrial cancer

Of all endometrial cancer patients 20?% are considered to be high risk patients. The recurrence rate is 50?%. According to the current German S2K guidelines in all patients presenting with a TNM stage Ib G3, II and III as well as all serous or small cell endometrial carcinomas, platinum chemotherapy with carboplatin/paclitaxel (AUC5 175 mg/m²) is indicated sequential to radiation. In the palliative situation local surgical treatment or radiation is the main option. A possible combination with either gestagens or cytostatic therapy depends on the hormone receptor status.

Vulvar cancer

Radiochemotherapy is indicated in inoperable situations, extensive recrudescence or in non-in sano resected patients. In metastasized patients the use of a combined chemotherapy is criticized due to the high toxicity and low response rate.     

Therapieoptionen in der Rezidivsituation des Endometriumkarzinoms

The treatment of women with recurrent endometrial cancer depends on the site relapse, with a distant recurrence being most common. Treatment options are hormonal therapy, cytotoxic chemotherapy, surgery and radiation therapy. Hormonal agents such as progestins are the first choice. Women with well differentiated tumors that express hormone receptors and remain progression free for an extended period show a favorable response. The average duration of response is only 4 months. Single agents such as doxorubicin, cisplatin/carboplatin and combination regimens of cytotoxic chemotherapy are used for women with aggressive and symptomatic disease. The response rates for combination regimes are higher than for monotherapy, with paclitaxel containing regimes improving survival when combined with doxorubicin and cisplatin. A combination of paclitaxel with carboplatin may be preferred because of lower toxicity. Recurrent serous or clear cell cancer can be treated similarly to epithelial ovarian cancer. Women with isolated vaginal cuff recurrences in previously non-irradiated cases have a chance of cure. The 5-year survival rates are 40–45%.