Elevation of interleukin-2 production in peripheral-blood lymphocytes by recombinant human granulocyte-colony-stimulating factor in ovarian-cancer patients during combination chemotherapy

Interleukin-2 (IL-2) production and peripheral blood lymphocyte (PBL) subsets were measured in ovarian cancer patients who received cis-platinum based chemotherapy with or without recombinant human granulocyte colony stimulating factor (rhG-CSF). Additional treatment with rhC-CSF resulted in significant elevation of IL-2 production and highly differentiated natural killer (NK) cell counts, indicating that rhG-CSF may be helpful for enhancement of the cellular immunity in ovarian cancer patients.     

Long-term survival of patients with advanced ovarian carcinoma treated with cisplatin-based chemotherapy regimens

Long-term results of different studies employing cisplatin-based chemotherapy in advanced ovara in cancer are just beginning to be published. Available data suggest that the rate of relapse decreases but does not cease, and the question of whether cisplatin-based chemotherapy results in an improved cure in advanced ovarian cancer is still unanswered. The long-term survival results published so far are reviewed. Furthermore the impact of other drugs, especially doxorubicin, in addition to cisplatin is discussed.     

Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy

Ninety ovarian carcinoma patients failing primary intravenous (IV) combination chemotherapy were treated with cisplatin-based combination intraperitoneal therapy. Sixty-five patients had residual disease greater than 2 cm at the start of intraperitoneal therapy. Their median survival was 8 months. Twenty-five patients had disease less than 2 cm; their median survival was greater than 49 months, and the survival curve has an apparent plateau at 69%, with no relapses having occurred after 32 months. The median survival for all 90 patients was 15 months. The median duration of follow-up for all patients was 37 months. These results confirm the critical role of tumor bulk in determining the effectiveness of intraperitoneal therapy, and suggest a role for intraperitoneal salvage treatment in patients with small-volume disease.     

晚期卵巢上皮癌新辅助化疗

晚期卵巢上皮癌预后很差,其主要预后因素为术后残留病灶大小.减少手术残留病灶,提高手术满意率,是每个妇科肿瘤医生的目标.提高手术满意率的手段之一是新辅助化疗(NACT),即术前辅助化疗.现就新辅助化疗的定义、适应证、方法及疗效作一综述.     

Linomide and interleukin-2 in patients with advanced renal cell carcinoma

Quinoline-3-carboxamide (Linomide) is a novel, synthetic immunomodulator acting via immunologic and non-immunologic mechanisms. It has shown efficacy against various malignancies, experimental autoimmune encephalomyelitis, and septic shock in animal models and has been investigated for clinical use in minimal residual myeloid leukemia with promising results. Interleukin-2 has shown considerable efficacy in palliative anti-tumor-treatment of advanced renal cell cancer, revealing remission rates of up to 40% in combination therapy regimens. Linomide is reported to exhibit synergistic effects with interleukin-2. Here we report on a clinical phase I/II study examining tolerance and efficacy of a combination therapy schedule of SQ interleukin-2 and PO Linomide in advanced renal cell cancer. Seventeen patients received 10 IU/m2 interleukin-2 per week for 8 weeks, resting interleukin-2 for another 8 weeks. In week 5 they started 5 mg Linomide daily, continued with 10 mg from week 7 to 16. No objective remissions were observed. Among 15 patients evaluable for response, 10 (66.7%) were progredient during the study. Three patients died during the observation period, including two not evaluable for response. Median survival was 4.0 months, median progression-free survival 2.5 months with a Kaplan-Meier estimate of 3.63 months. Fever, reduced general condition, nausea/vomiting, dyspnea, anorexia, chills and hypotension were the most common side effects, reaching WHO grade 3 in 6 and grade 4 in 2 cases. In summary, Linomide in combination with interleukin-2 provides no advantages in efficacy or toxicity over other therapy regimens employing interleukin-2.     

Timing of surgery and the role of cytoreductive chemotherapy in patients with advanced ovarian carcinoma

We retrospectively selected 27 consecutive patients with advanced ovarian carcinoma (15 stage III, 11 stage IV and 1 relapse) who had an unresectable intraabdominal tumor at presentation and prospectively evaluated the overall treatment outcome. Patients were initially treated with chemotherapy consisting of cisplatin-containing regimens in 20 cases, adriamycin and cyclophosphamide in 5, and melphalan in 2. Treatment was continued until maximal tumor response or progression. Following a median of 6 cycles of chemotherapy, all patients underwent debulking surgery. Six women were without evidence of disease and 13 had minimal residual disease after surgery, for an overall 70% rate of optimal debulking. Patients with evidence of disease at laparotomy were treated with 5 additional cycles of chemotherapy, and response was then assessed at laparotomy except for patients with progressive disease. Nine (33%) patients were pathologic complete responders at the end of the entire treatment program. Overall median survival time was 26 months, with a median relapse-free survival of 33 months. Tumor responses were not associated with any particular chemotherapy regimen. The results achieved in this series of patients together with the data from the literature suggests that use of a cytoreductive chemotherapy of short duration has the potential of increasing the rate of optimal debulking surgery. Furthermore, it may contribute to a better disease control in women with bulky ovarian carcinoma compared to the present strategy, which consists of surgery followed by chemotherapy.     

Multimodality treatment of patients with advanced ovarian carcinoma

A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.     

Randomised trial comparing prednimustine with combination chemotherapy in advanced ovarian carcinoma

Summary A total of 76 patients with advanced epithelial ovarian carcinoma were randomised to receive 6 months of treatment with either a combination of hexamethylmelamine, 5-fluorouracil, cisplatin and prednimustine or prednimustine alone following initial surgery. Pathologically confirmed response rates were 35% for combination chemotherapy and 28% for prednimustine, and the overall survival was identical for the two groups. Seven patients achieved a pathologically defined complete response, one of whom relapsed at 8 months; the others remain disease-free 18–36 months (median, 23 months) after presentation. The extent of initial surgery significantly affected the survival of patients receiving prednimustine but not of those receiving combination chemotherapy. Prednimustine can produce durable responses in advanced ovarian cancer using a schedule that results in negligible toxicity.     

Effects of chemotherapy of advanced malignant ovarian tumors

Malignant ovarian tumor is regarded as the disease with the worse prognosis among obstetrical and gynecological malignancies. In the past, a great number of trials have been done with single or combined treatments. Because of the rather low incidence of malignant ovarian tumor in any one hospital over a short period of time and the numerous factors affecting the prognosis of patients, no definite procedures have been established so far. In order to evaluate the effects of chemotherapy, 460 cases were investigated retrospectively. These cases were treated primarily with surgery from 1974 to 1979 and adjuvant chemotherapy was selected freely by the doctors responsible. Cumulative 5-year survival rates were calculated as 88.8% for a low potential malignant group, 65.9% for stage I ovarian cancer, 40.6% for stage II, 9.7% for stage III, 0% for stage IV and 10% for metastatic tumor from other organs. The effects of chemotherapy were investigated especially for stage III and IV and the metastatic tumor group. Cumulative survival curves were justified by generalized Wilcoxon test. An MFC combination, a double-agent, a single-agent and a no-chemotherapy group were compared by survival curves. There were statistical significances between the MFC and no-chemotherapy group, and the double-agent and no-chemotherapy group. Significant tendency was present between the MFC and single-agent group. Several popularly-used combinations in this period such as MFC, VEM, METT, FAMT, METVFC and a group with other combinations were compared. There were no statistical significances among the 6 combinations, but an MFC combination seemed to be a better treatment for malignant ovarian tumors judging from accumulative survival curves.     

Venous thromboembolism,interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma

BackgroundWe compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels.MethodsA multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined.FindingsPatients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P < 0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P = 0.006). Advanced OCCC (hazard ratio [HR] 3.38, P < 0.0001), thrombocytosis (HR 1.42, P = 0.032) and elevated IL-6 (HR 8.90, P = 0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P < 0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P < 0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P = 0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P = 0.07).InterpretationAdvanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.     

A case of brain metastasis from advanced ovarian clear-cell carcinoma during maintenance chemotherapy with irinotecan+cisplatin

Clear-cell carcinoma of the ovary is a highly malignant neoplasm. Survival of patients in the advanced stage is poor, and the best treatment is not clear. We report here a case of a 57-year-old woman who had Stage IIIb advanced clearcell carcinoma of the ovary. We performed abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lympho adenectomy and partial omentectomy. After the operation she was placed on induction and maintenance chemotherapy with a combination of irinotecan(CPT-11)(60 mg/m2, day 1, 15)plus cisplatin(CDDP)(60 mg/m2, day 1). Four years after surgery, a metastatic tumor was found in the brain. Considering the poor prognosis of clear-cell carcinoma, this regimen is thought to be effective for advanced clear-cell carcinoma of the ovary. It is important to check brain metastases under maintenance chemotherapy.     

Intraperitoneal chemotherapy through implantable injection port in patients with advanced ovarian (or tubal) carcinoma

A total of 38 cycles of intraperitoneal chemotherapy through implantable injection port were carried out in 9 patients with advanced or recurrent ovarian (tubal) carcinoma. The combination chemotherapy consisted of cisplatin 100 mg or carboplatin 450 mg, 5-FU 500 mg and OK-432 10 KE was administered every four weeks for a total of six cycles. Clinical response was evaluated after chemotherapy. Of the eight evaluated patients (in one patient chemotherapy is not completed yet), 1 had complete response, 3 partial response, 2 stable disease and 2 progressive disease. Therapy-related toxic effects were moderate, consisting chiefly of myelosuppression that seemed dose limiting.     

节律化疗作为体力状况较差的晚期卵巢上皮癌患者的姑息治疗

Objective  

The aim of our study was to evaluate the clinical efficacy and tolerability of metronomic chemotherapy in patients with advanced ovarian carcinoma.     

晚期卵巢癌化疗联合放疗的临床研究

目的探讨化疗联合放疗综合治疗晚期卵巢癌的疗效和毒性。方法随机将不能手术的晚期卵巢癌患者分为两组,即化疗组和化放疗组,两组各36例,均使用IPA方案,IF01.2g/m2,i.vdripd1~5,Mesna0.4gi.v(0、4、8h)d1~5,DDP60~80mg/m2,i.vd1,ADM40~60mg/m2,i.vd1。化疗组用该方案连续化疗3个周期,每3周重复1次;化放疗组先用该方案化疗1周期,接着用6MV-X线全盆腔外照射DT40GY/4W,再缩野至癌灶局部加量DT10~20GY/1~2W,放疗结束后,休息1周,再化疗2个周期,每3周重复1次。结果化疗组和化放疗组有效率(CR PR)为77.8%和100%,1、3年生存率分别为60.1%,32.7%和73.1%,48.2%。毒性反应以骨髓抑制和消化道反应为主。结论化疗联合放疗综合治疗晚期卵巢癌能提高局控率和生存率,且并发症发生率较低,是一种安全、有效、较理想的治疗方法。     

高龄晚期胃癌化疗的临床研究

目的：探讨化疗对高龄晚期胃癌患者的疗效与安全性。方法：研究我院88例高龄晚期胃癌初治患者,根据是否接受化疗,分为化疗组43例,对照组45例。化疗组分别应用FOLF0x4方案、cF方案、优福定单药方案、卡培他滨单药方案、多西他赛联合卡培他滨方案,至少完成3个周期化疗;对照组予最佳对症支持治疗。结果：化疗组与对照组有效率分别为44．19％、2．22％,差异有统计学意义（P〈0．01）;生活质量改善获益分别为83．72％、57．78％,差异有统计学意义（P〈0．01）;中位疾病进展时间分别为（5．3±1．09）个月、（3．5±0．22）个月,差异有统计学意义（P〈0．05）;中位生存时间分别为（10．20±1．442）个月、（7．40±0．803）个月,差异有统计学意义（P〈0．05）。化疗毒副反应仅有1／43（2．3％）Ⅳ度血液学毒性,经对症治疗后好转。结论：化疗组的有效率、生活质量改善获益率、中位疾病进展时间、中位总生存期均较最佳对症治疗组有显著差异,且毒副反应轻微,患者能耐受治疗,提示对于高龄晚期胃癌患者化疗在延长生存期、提高生活质量等方面明显优于最佳对症支持治疗。     

新辅助化疗在中晚期卵巢癌的应用探讨

目的:探讨新辅助化疗对中晚期卵巢癌患者复发和预后的影响。方法:回顾性分析52例中晚期卵巢癌患者的治疗及预后,32例术前采用全身序贯化疗(standard sequence chemotherapy SSC) 腹腔内灌注化疗2个疗程。术后用DNA原位末端标记检测肿瘤细胞凋亡并随访观察癌复发和生存时间。结果:新辅助化疗组与未术前化疗组肿瘤细胞凋亡数分别为(50.71;3.87)和(29.13;3.69)个?高倍视野,观察组1、3、5年复发率为12.5%(4/32)、25%(8/32)、59.4%(19/32);生存率100%(32/32)、78.1%(25/32)、22%(7/32)。对照组1、3、5年复发率35%(7/20)、45%(9/20)、90%(18/20);生存率80%(16/20)、55%(11/20)、20%(4/20)。3年生存率的比较中,化疗组为25例,明显高于无术前化疗组11例,P<0.05,差异有显著意义。而5年生存率差,P>0.05异则无显著意义。术前化疗组中,腹痛腹胀等症状缓解率为30%,肿块缩小率(PR CR)为62.5%,基本切净率为93%。残留>2cm有2例。无术前化疗组中,基本切净率为85%,残留>2cm有3例,相比,P<0.05,差异有显著意义。结论:新辅助化疗对卵巢癌细胞有明显促凋亡作用,是预防癌复发转移和改善预后的有效手段。     

新辅助化疗在中晚期卵巢癌的应用探讨

目的：探讨新辅助化疗对中晚期卵巢癌患者复发和预后的影响。方法：回顾性分析52例中晚期卵巢癌患者的治疗及预后,32例术前采用全身序贯化疗（standard sequence chemotherapy SSC）＋腹腔内灌注化疗2个疗程。术后用DNA原位末端标记检测肿瘤细胞凋亡并随访观察癌复发和生存时间。结果：新辅助化疗组与未术前化疗组肿瘤细胞凋亡数分别为（50.71;3.87）和（29.13;3.69）个？高倍视野,观察组1、3、5年复发率为12.5%（4/32）、25%（8/32）、59.4%（19/32）;生存率100%（32/32）、78.1%（25/32）、22%（7/32）。对照组1、3、5年复发率35%（7/20）、45%（9/20）、90%（18/20）;生存率80%（16/20）、55%（11/20）、20%（4/20）。3年生存率的比较中,化疗组为25例,明显高于无术前化疗组11例,P〈0.05,差异有显著意义。而5年生存率差,P〉0.05异则无显著意义。术前化疗组中,腹痛腹胀等症状缓解率为30%,肿块缩小率（PR＋CR）为62.5%,基本切净率为93%。残留〉2cm有2例。无术前化疗组中,基本切净率为85%,残留〉2cm有3例,相比,P〈0.05,差异有显著意义。结论：新辅助化疗对卵巢癌细胞有明显促凋亡作用,是预防癌复发转移和改善预后的有效手段。     

Five-year results of cyclic semi-high dose neoadjuvant chemotherapy supported by autologous peripheral blood stem-cell transplantation in patients with advanced ovarian cancer

Background To achieve anti-ovarian tumor responses similar to those obtained with high-dose chemotherapy but with milder side effects, we developed a treatment protocol in which semi-high dose multi-cycle neoadjuvant chemotherapy was supported by autologous peripheral blood stem-cell transplantation (auto-PBSCT).Methods Seventeen patients with advanced ovarian cancer were enrolled in this study. Two cycles of semi-high dose neoadjuvant chemotherapy, using carboplatin (AUC, 8.75; average dose, 621mg/m²) and etoposide (average dose, 960mg/m²) were supported by auto-PBSCT and followed by cytoreductive surgery and further chemotherapy. Each patient was followed for at least 5 years.Results This treatment schedule achieved an overall response rate of 70.6% in 17 patients with stage III or stage IV ovarian cancer. The 5-year disease-free survival rate was 52.9% (95% confidence interval, 29.2%–76.6%) and the median survival time was 63 months (95% confidence interval, 16–79 months). Thus, we obtained superior treatment outcomes in these 17 patients in comparison with published conventional protocols.Conclusion Cyclic semi-high dose neoadjuvant chemotherapy supported by auto-PBSCT may be tolerable and favorable for patients with advanced ovarian cancer.     

Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK

The protein-bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non-reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10-100 micrograms/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK-induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK-induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha-chain or beta-chain of IL-2 receptors (IL-2R) had no effect on PSK-induced ATK activity. Supernatants from PSK-stimulated lymphocyte cultures did not induce ATK. Cell fractionation experiments revealed that CD3-CD16+ large granular lymphocytes (LGL) and/or CD3+CD16- T lymphocytes were responsible for both spontaneous and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL-2/IL-2R systems.