Chemotherapy in ovarian carcinoma recurrent after radiation therapy

Fifty-seven patients referred to Roswell Park Memorial Institute between 1971-1975 with Stage III or IV epithelial ovarian cancer treated with prior radiation therapy were randomly allocated to treatment with melphalan, 5-fluorouracil (5-Fu) plus melphalan (FUME), actinomycin-D plus 5-fluorouracil plus melphalan (ACFUME), actinomycin-D, or 5-fluorouracil plus cyclophosphamide (ACFUCY). These patients receiving 5-FU plus melphalan had longer median duration of survival with better quality of life. Combination chemotherapeutic agents effected significantly. better responses (P less than 0.05) than single agent chemotherapy. The ACFUME and ACFUCY combinations resulted in higher incidence of severe and life-threatening toxicity. Patients showing complete response had maximum median duration of survival.     

Chemotherapy for advanced epithelial ovarian carcinoma

Advanced epithelial ovarian cancer (AOC) is the most common clinical presentation of ovarian cancer. Virtually all patients will require some form of chemotherapy with curative or palliative intent. Prognostic factors, first- and second-line therapy, as well as experimental approaches for AOC are reviewed.     

Chemotherapy induces death receptor 5 in epithelial ovarian carcinoma

OBJECTIVES: Defects in the apoptotic pathway are a general cause for drug resistance. Chemotherapy in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has proven to be an effective strategy to induce apoptosis in vitro in ovarian tumor cells. Systemic TRAIL administration might be a therapeutic option, since no toxicity was observed in nonhuman primates. In the present study, expression of TRAIL and its apoptosis-inducing death receptors (DR4 and DR5) and inhibitory decoy receptor (DcR1) was studied in normal ovaries and in malignant ovarian tumors before and after chemotherapy to investigate the therapeutic potential of TRAIL. METHODS: DR4, DR5, DcR1, and TRAIL were studied immunohistochemically in 5 normal ovaries, 15 stages I/II, and 26 stages III/IV primary ovarian cancers, including 19 paired tumor samples (pre- and post-chemotherapy). RESULTS: Surface epithelium of normal ovaries expressed TRAIL and its receptors; ovarian stromal cells expressed only DcR1. Of the ovarian cancers, 73% expressed DR4, 51% DR5, 46% DcR1, and 34% TRAIL. Most primary ovarian cancers (88%) expressed at least one death receptor. TRAIL expression was lower in stage III/IV than in stage I/II tumors (P<0.05). In paired samples, DR5 immunostaining was more frequently (P=0.05) and stronger (P<0.01) expressed in residual tumors. CONCLUSION: Early stage tumors expressed TRAIL more frequently than advanced stage tumors. Most primary and residual ovarian tumors expressed at least one TRAIL death receptor, while in residual tumors following chemotherapy, DR5 was more frequently expressed. Therefore, human recombinant TRAIL administration might be an interesting treatment option.     

Tamoxifen therapy in recurrent epithelial ovarian carcinoma

Thirty-seven patients with recurrent epithelial ovarian carcinoma were entered into a trial of tamoxifen therapy (10 mg BID) to determine the effect on long-term survival. Thirty-one patients were evaluable with follow-up ranging from 6 to 42 months since initiation of hormonal therapy. All patients were heavily pretreated with multiple chemotherapeutic regimens (median 3). There was 1 complete responder (3.2%), 2/31 (6.4%) had a partial response, 6/31 (19.3%) had stable disease, and 22/31 (71%) had progressive disease. Twenty-four patients are dead (23 from advanced carcinoma, 1 from cardiac causes); 5 patients are alive with disease; 2 patients are lost to follow-up. Median survival of nonresponders was 7 months versus 16 months for responders (CR + PR + stable disease) (P = 0.001 life table analysis). Of the 9 responders, 7 had poorly differentiated tumors (grades 3 or 4), and 2 had moderately differentiated tumors (grade 2). Eleven patients had estrogen and progesterone receptor studies (ER, PR). No correlation between response rate and receptor status was evident. We conclude that although significant disease regression is unlikely to result from tamoxifen therapy, there may be a subset of patients who can benefit from the cytostatic properties of hormonal manipulation.     

复发性卵巢上皮性癌的诊断及处理

目的 探讨复发性卵巢上皮性癌的诊断、治疗方法及其预后。方法 将52例复发性卵巢上皮性癌患者分为5组,手术 化学药物治疗(化疗)组,共26例;单纯化疗组,共14例;手术 化疗 放射治疗(放疗)组,共4例;手术 放疗组,共4例;未治组：4例。对复发性卵巢上皮性癌的诊断方法和各组间生存时间进行比较。结果 复发性卵巢上皮性癌的诊断方法其阳性诊断率依次为,妇科检查(妇检)73．1％,B超84．6％,CA12553．8％,妇检、B超和CA125联合检测阳性率为70．5％。手术 化疗组、单纯化疗组的中位数生存时间分别为11个月和12个月。手术 化疗 放疗组的生存时间为10～12个月。手术 放疗组的生存时间为14～25个月。结论 妇检、B超和CA125的联合检测有助于提高复发性卵巢上皮性癌的诊断阳性率。在复发性卵巢上皮性癌治疗中,手术的作用有待进一步研究证实,化疗具有很好的作用,放疗的作用和地位应引起注意。     

Intraperitoneal chemotherapy strategies in the treatment of epithelial ovarian carcinoma

The intraperitoneal delivery of chemotherapeutic agents is presently being investigated as a part of salvage treatment for epithelial ovarian cancer. There are several promising new agents that appear to demonstrate a benefit in selected patients.     

Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma

OBJECTIVE: Hormone replacement therapy (HRT) has been inconsistently linked to ovarian cancer. Estrogen formulations in HRT vary in their effects on estrogen-sensitive target tissues, such as the ovary. The aim of the study is to evaluate the impact of various HRT formulations and their characteristics of use on the risk of epithelial ovarian carcinoma (EOC). METHODS: We assessed the association between the use of HRT and the risk of invasive EOC in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or above at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interview by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Multivariate unconditional logistic regression analyses were used to adjust for age at diagnosis, number of live births, use of oral contraceptives, family history of ovarian carcinoma, and history of tubal ligation. RESULTS: Overall, no association was found between any use of HRT and EOC. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction = 0.049). No significant differences in EOC risk were observed for other HRT formulations. CONCLUSIONS: Our results did not suggest any consistent pattern of altered risk for EOC and the overall use of HRT by specific formulations of HRT.     

Whole abdominal radiation as salvage therapy for epithelial ovarian cancer

Thirty patients found to have residual epithelial ovarian cancer at second-look laparotomy were treated with whole abdominal radiation as salvage therapy. Dosage fractions were 120 rad per day until 3000 rad were delivered, then the pelvis was boosted to 5000 rad at 180 rad per day. Fourteen patients (47%) completed therapy without interruption and seven (23%) completed therapy with interruptions due to myelosuppression ranging from one to four weeks. Therapy was not completed in nine patients (30%). Four of 16 patients (25%) with microscopic residual disease before radiation remain alive and free of disease at 22 to 41 months. Two of six (33%) patients with minimal (less than or equal to 5 mm) residual disease remain alive and free of disease 19 to 40 months after radiation treatment. Patients with residual nodules greater than 5 mm uniformly did poorly. Patients who progressed on primary chemotherapy had a median survival of seven months, compared with more than 38 months for chemotherapy responders. Chronic bowel morbidity was a significant problem, with 30% of patients surviving at least four months from completion of radiation requiring laparotomy for small bowel obstruction. These preliminary results suggest that whole abdominal radiation may be useful in the management of patients who have responded to primary chemotherapy, but the benefit is confined to those patients who have minimal or microscopic disease at second-look laparotomy.     

Whole-abdomen radiation as a second-line therapy for epithelial ovarian cancer

Whole-abdomen irradiation was delivered to 11 patients with persistent epithelial ovarian cancer after chemotherapy. Ten of the eleven patients have recurred and subsequently died of disease. The median time to recurrence was 5.5 months. All 10 recurrences were within the irradiated field. All 6 patients with microscopic disease at second-look laparotomy recurred. Four of the five patients with minimal residual disease (less than or equal to 5 mm) at second-look laparotomy recurred. One patient is alive with no evidence of recurrence at 14 months. Four patients developed small bowel obstruction, three of which were associated with recurrence. During therapy, 4 patients developed significant enteritis and 5 patients developed significant bone marrow suppression. All 11 patients completed radiation therapy, although in 4 there were interruptions of 1 to 3 weeks. Whole-abdomen irradiation does not appear to be an effective second-line regimen for epithelial ovarian cancer, even in the presence of microscopic or minimal residual disease.     

High dose chemotherapeutic strategies in the treatment of epithelial ovarian carcinoma

High dose chemotherapy with stem cell rescue has been used in an attempt to overcome chemotherapy resistance and increase survival in patients with poor prognosis epithelial ovarian cancer. Untreated patients with advanced stage disease and those with chemosensitive recurrent disease do better in terms of response rates as well as duration of response and overall survival. Newer strategies using multiple cycles of dose intense therapy may improve results although it will be difficult to document changes in the natural history of advanced ovarian cancer without the completion of randomized phase III trials.     

Changes in the histocytological grading of epithelial ovarian carcinoma following treatment

Although the microscopic grade of epithelial ovarian carcinoma is recognized as an important prognostic factor, the grading systems are still controversial. A cytohistological grading system is described using the sum of the scores (from 1 to 4) of eight histological and cytological features. This grading is applied to the initial surgical specimens of 37 patients seen at UCLA Center for the Health Sciences; it is also used for evaluation of pathologic specimens obtained at subsequent laparotomies. The evolution of the score at subsequent laparotomies (stable, increasing, or decreasing) is correlated with the type of therapy, response to treatment, and prognosis. An increasing score at the second-look laparotomy is a poor prognostic factor with a significantly shorter patient survival (p less than 0.05). The tumor score at second-look laparotomy is significantly increased in cases of macroscopically positive operation (p less than 0.05) and tumor progression (p less than 0.001). The type of therapy has no significant effect on the tumor score. A multivariate analysis shows that a decreasing score is related to a lower mitotic activity. Conversely, an increasing score is related to a change in tumor pattern. This study demonstrates the prognostic value of our grading system, which needs to be further validated by prospective studies.     

Tumor markers of epithelial and stromal cell origin at second-look laparotomy in ovarian carcinoma

The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical examination were evaluated in association with 48 second-look laparotomies of ovarian carcinoma patients treated with cytotoxic chemotherapy. At laparotomy, there were 23 macroscopical and 6 microscopical tumors. Nineteen patients were disease-free. Clinical examination, CA 125, and PIIINP were correctly positive in 93, 92, and 82% of cases, respectively. When CA 125 and PIIINP were used simultaneously this value increased to 100%. The sensitivity of CA 125 (43%) and PIIINP (56%) was unsatisfactory, but with their combination it increased to 62%. The use of CA 125, PIIINP, or both increased the sensitivity of clinical examination by 14, 24, and 27%, respectively. Of all the occult tumors, CA 125 detected 33%, PIIINP 57%, and both 66%. The detection rate of macroscopical tumors missed at clinical examination by both was 71%. Hence, PIIINP may be a clinically valuable complement to CA 125 and clinical examination before second-look laparotomy.     

Hyperfractionation of whole-abdomen radiation therapy: salvage treatment of persistent ovarian carcinoma following chemotherapy

Whole-abdomen radiation therapy has been utilized as primary adjunctive therapy in the management of epithelial ovarian carcinomas with encouraging results. The results reported when using standard fractionation protocols in patients with recurrent or persistent ovarian carcinoma have been poor and treatment-related toxicities have been severe. There are reported theoretical and clinical advantages of hyperfractionation of ionizing radiation in treating malignancies. Fifteen patients have been treated with a twice-a-day whole-abdomen, open-field radiation technique delivering 80 cGy per fraction, to a total dose of 3040 cGy in 19 treatment days. All patients had Stage III epithelial ovarian carcinoma with persistent disease detected at pretreatment laparotomy after cis-platinum-based chemotherapy. All patients had moderately to poorly differentiated tumors with residual disease less than 1 cm. Acute side effects of treatment included mild to moderate nausea and diarrhea. Thrombocytopenia (less than 50,000) was noted in five patients. No bleeding or infectious complications were noted, and no patient required hospital admission for side effects. Disease recurred in nine patients with two still alive 13 and 52 months after starting irradiation. Six patients are currently alive without evidence of disease at follow-up, ranging from eight to 48 months. The mean survival to date is 20 months with four patients alive more than 2 years, and two patients alive for greater than 3 years from their radiation therapy. Patient tolerance has been acceptable, and both the short and long-term toxicities are minimal. Late side effects of treatment have not been noted. This technique offers a chance for a long, disease-free interval and possible cure in well-defined cases of chemotherapy-treated patients with persistent ovarian carcinoma.     

综合性治疗复发性卵巢上皮性癌的疗效及预后分析

目的　探讨个体化、分阶段综合治疗复发性卵巢上皮性癌 (卵巢癌 )的疗效 ,及分析影响预后的因素。方法　对 70例卵巢癌分两个阶段进行治疗 ,第一阶段为诱导缓解治疗阶段 ,即对铂类药物敏感患者选用紫杉醇 顺铂 (TP)或卡铂 环磷酰胺 (CP)方案进行化疗 ;对铂类药物耐药患者选用紫杉醇 丝裂霉素 (TM)或足叶乙甙 丝裂霉素 (VM)二线药物化疗方案进行化疗。化疗后行二次肿瘤细胞减灭术 ,使残留癌灶直径≤ 1cm。对经化疗或合并二次肿瘤细胞减灭术获得临床缓解的患者 ,进行残留癌灶局部放疗。第二阶段为巩固治疗阶段 ,即对获得临床缓解的患者采用间断、小剂量化疗 ,在化放疗期间选用干扰素等免疫治疗。结果　 70例患者的 1～ 5年总生存率分别为 6 7%、5 1%、4 5 %、38%、32 % ,中位生存期为 38 5 7个月 ;1～ 3年无癌生存率分别为 4 1%、37%、2 4 % ,中位无癌生存期为 12 0 0个月。多因素分析结果显示 ,中位停用铂类药物治疗时间 (P <0 0 5 )、Karnofsky评分 (P <0 0 1)、残留癌灶大小 (P <0 0 1)及化疗次数 (P <0 0 5 )等 ,是卵巢癌复发后生存期的独立预后影响因素 ,而残留癌灶大小 (P <0 0 5 )及化疗次数 (P <0 0 1) ,是卵巢癌复发后无癌生存期的独立预后影响因素。结论　个体化、分阶段的综合治疗     

晚期卵巢上皮性癌的综合治疗和预后分析

目的：对晚期卵巢上皮性癌的综合治疗进行研究,并对其预后因素加以分析,方法：选择复旦大学附属肿瘤医院1998年1月至2000年12月收治的晚期卵巢上皮性癌患者53例（研究组）,给予综合治疗即诱导缓解,巩固治疗和免疫支持治疗,另选择1986年1月至1997年、12月间收治的晚期卵巢上皮性癌患者318例（对照组）,给予肿瘤细胞减灭术及常规化学药物治疗（化疗）。结果：研究组的完全缓解率,部分缓解率分别为90．6％,5．7％,均明显高于对照组的70．1％,5．3％（P＜0．01）,研究组的1,2,3年生存率分别为97．7％,89．1％,83．6％,均明显高于对照组的71．8％,44．1％,29．8％（P＜0．01）,研究组的1,2,3年无癌生存率分别为92．6％,70％,75．0％,均明显高于对照组的60．3％,37．8％,28．6％（P＜0．01）,研究组1,2年的肿瘤复发率分别为7．5％,25．0％,均明显低于对照组的39．7％,62．2％（P＜0．01）,和预后有关的因素有年龄,首治医院,手术病理分期,腹水,病理分化程度,术前化疗,术后腹腔化疗和静脉化疗,和无癌生存相关的预后因素是首治医院,卵巢侵犯程度,残留癌直径大小和术后腹腔化疗,结论：通过诱导缓解,巩固治疗和免疫支持治疗可提高疗效,明显降低了晚期卵巢上皮性癌的1,2年复发率,提高了晚期上皮性癌的生存率。     

Chemotherapy in the treatment of ovarian carcinosarcoma

Carcinosarcoma of the ovary is a rare neoplasm representing 1% of this organ malignancies. The disease appears almost exclusively in advanced stage having an unfavourable prognosis. Three patients affected by carcinosarcoma (MMMT) of the ovary admitted to our Operative Unit have been treated. All patients underwent surgery and subsequently chemotherapy. Two patients were affected by heterologous MMMT and were stage IV and IIIc respectively, the other one, affected by homologous MMMT, was stage IIIc. Stage IV patient was submitted to 6 cycles of CARBO + IFX + CDDP, second look and further 6 cycles of TAX. After 23 months she was submitted to colostomy for intestine occlusion. At the 35 months she died for cachexia and intestine occlusion. Stage IIIc heterologous patient was submitted to 6 cycles of CDDP + EPI + IFX + MESNA for 3 days; at 6 months from diagnosis she did not present any sign of disease. Stage IIIc homologous patient, affected by chronic renal insufficiency and submitted to dialysis, underwent 5 cycles of TAX and at 11 months from diagnosis presented partial response. Carcinosarcoma of the ovary, because of its rarity, and of the poor record of cases in the literature, is a much debated topic in particularitis complementary therapy. Opinions of the several authors are in contrast regarding the use of CHT + RT at the same time. Only RT after surgery does not seem to improve the survival of these patients. Personal experience, with the reported outlines, compared with survival, seems to confirm the use of CDDP and of IFX and to give new horizons to TAX, waiting for further findings.