吉西他滨联合奈达铂与紫杉醇治疗顺铂耐药的转移性鼻咽癌

 目的　观察吉西他滨联合奈达铂与紫杉醇治疗对顺铂耐药的转移性鼻咽癌的近期疗效及不良反应。 方法　15例顺铂方案化疗失败的转移性鼻咽癌患者。吉西他滨1000 mg／m2,第1、8天;奈达铂70 mg／m2,第1天;紫杉醇135 mg／m2,第1天;21 d为1个疗程,疗效评价采用RECIST 3.0标准。结果　全组15例患者CR 1例 ,PR 5例 ,SD 6例 ,PD 3例 ,总有效（CR+PR）率40.0 %。中位TTP为4.7个月,中位生存期为6.3个月。主要不良反应为血液学毒性,Ⅲ＋Ⅳ度骨髓抑制的发生率分别为：白细胞减少40.0 %、贫血6.7 %、血小板减少20.0 %。其他不良反应轻微。结论　吉西他滨联合奈达铂与紫杉醇的化疗方案可作为顺铂耐药转移性鼻咽癌的二线方案。     

Activity of aphidicolin glycinate alone or in combination with cisplatin in a murine ovarian tumor resistant to cisplatin

Summary Aphidicolin, a reversible inhibitor of DNA polymerase and , has recently been reported to reverse the resistance to cisplatin (DDP) of an ovarian cancer cell line. We investigated the pharmacokinetics of aphidicolin in mice and examined its activity either alone or in combination with DDP in the DDP-sensitive M5076 (M5) murine reticular cell sarcoma as well as in a DDP-resistant subline (M5/DDP). The drug was cleared from plasma very rapidly (clearance, 41.6 ml min^–1 kg^–1), showing a half-life of 15 min. Aphidicolin concentrations in the tumor were approximately 50% of those found in plasma at steady state. Using several dose schedules and continuous infusions we failed to detect significant antitumor activity for aphidicolin glycinate. Potentiation of the activity of DDP by aphidicolin glycinate was moderate in mice bearing M5 tumor as well as in those bearing M5/DDP tumor. These data do not support the possible clinical use of aphidicolin in combination with DDP. However, further studies should be carried out in different tumor models before this possibility is conclusively ruled out.This work was supported by the Italian Association for Cancer Research, Milan, and by a Trafik fellowship (awarded to G. T.) and a F. B. fellowship (awarded to G. D.)     

Combination chemotherapy with Hemzar (gemcitabine) and cisplatin for relapsing and cisplatin-resistant ovarian cancer

The paper is concerned with the data on treatment of 33 patients with advanced ovarian cancer, aged 34-72 (average age of 52.5). Having received numerous regimens of combination chemotherapy, mainly, with cisplatin-containing drugs, sixty-one percent had visceral metastases. Early-onset relapse was in 18.2%, late-onset--12.1% and primary refractory to cisplatin chemotherapy--30%. Hemzar (hemcytabin) + cisplatin + carboplatin treatment was given in 15- or 8-day courses (hemzar--1,000 mg/m2, day 1, 8 and 15 or day 1 and 8; cisplatin m2 or carboplatin AVC5--60 mg/m2, day 1 or 15, day 1 or 8, respectively). A total of 102 cycles of therapy were given and evaluated. Complete response was reported in 2 (6.0%), partial--5 (15.2%), and stabilization--13 (39.4%); significant clinical effect--60.6%. Such side-effects as leukemia stage I-II--63.6%; stage III-IV--3%, neutropenia stage I-II--39.4; stage III-IV--24.2%, thrombocytopenia stage I-II--6%, and asthenia stage I-II--12.1%, stage III-IV--3 patients, did not interfere with treatment. Combination chemotherapy with hemzar + cisplatin + carboplatin was effective and sufficiently tolerable. It is indicated in management of relapse and primary resistance to cisplatin drugs administered for ovarian cancer whenever all other remedies have failed.     

Combination chemotherapy of paclitaxel and cisplatin induces apoptosis with Bcl-2 phosphorylation in a cisplatin-resistant human epidermoid carcinoma cell line

PURPOSE: Paclitaxel (Taxol, TXL) is an antimicrotubule agent that stabilizes microtubules, arrests the cell cycle at the G(2)/M phase and induces apoptosis. In vitro drug sensitivity assays have shown that the combination of TXL and CDDP is more effective in CDDP-resistant ovarian carcinoma cell lines, with different cytotoxicities depending on the sequence of drug exposure. CDDP also shows poor results in human epidermoid carcinoma particularly of the head and neck region. METHODS: We investigated the effects and the molecular mechanisms of combination chemotherapy with TXL and CDDP in the CDDP-resistant cell line A431/CDDP2, and in its parental human epidermoid cell line A431/P. Drug sensitivity was determined using the MTS assay and cell cycle perturbation was analyzed using flow cytometry. DNA fragmentation was then analyzed and the protein levels of caspase-3 and Bcl-2, and phosphorylated of Bcl-2 were determined by Western blotting. RESULTS: In the drug sensitivity assay, exposure to CDDP prior to TXL was more effective than exposure TXL prior to CDDP in A431/P cells. In A431/CDDP2 cells, exposure to TXL prior to CDDP was more effective than exposure to CDDP prior to TXL. Exposure to TXL arrested the cells in the G(2)/M phase in both cell lines. In A431/CDDP2 cells, exposure to TXL prior to CDDP arrested the cells in the G(2)/M phase, an effect caused by either CDDP or TXL. Analysis of DNA fragmentation showed similar results to the drug sensitivity assay. Expression of caspase-3 protein active form was detected following exposure to TXL only and to the TXL/CDDP combination in both A431/P and A431/CDDP2 cells, but phosphorylation of Bcl-2 protein was detected only following exposure to TXL and only in A431/CDDP2 cells. CONCLUSIONS: These results indicate that exposure to TXL prior to CDDP plays a key role in circumventing CDDP resistance by phosphorylating Bcl-2 protein in the human epidermoid carcinoma cell line A431/CDDP2.     

Hepatocyte growth factor sensitizes human ovarian carcinoma cell lines to paclitaxel and cisplatin

The hepatocyte growth factor (HGF) receptor, encoded by the MET oncogene, is expressed in approximately 70% of human ovarian carcinomas and overexpressed in 30% of cases. Because HGF is known to protect cells from apoptosis, we investigated whether receptor expression modifies ovarian cancer cell response to chemotherapy. The apoptotic effect of the front-line chemotherapeutic drugs paclitaxel and cisplatin on cells treated with HGF was studied. In ovarian cancer cell lines, pretreatment with HGF surprisingly enhances the apoptotic response to low doses of paclitaxel and cisplatin. HGF empowers specifically the intrinsic apoptotic pathway, whereas it protects cells from extrinsic Fas-induced apoptosis. Chemotherapy sensitization is specific for HGF because another growth factor (e.g., epidermal growth factor) increases ovarian cancer cell survival. In nonovarian cancer cell models, as expected, HGF provides protection from drug-induced apoptosis. These data show that HGF sensitizes ovarian carcinoma cells to low-dose chemotherapeutic agents. This suggests that HGF may be used to improve response to chemotherapy in a set of human ovarian carcinomas molecularly classified based on the MET oncogene expression.     

Weekly paclitaxel and cisplatin in recurrent ovarian cancer

This study was performed to assess the feasibility of weekly paclitaxel (TXL) and cisplatin (CDDP) in patients with recurrent ovarian cancer. Ten of eleven patients experienced recurrence after more than 6 months after first line CDDP-based chemotherapy. TXL and CDDP were given at initial doses of 60 mg/m2 and 30 mg/m2 on days 1, 8, and 15 in 2 patients and an increase in the respective dose level was planned to 60/35 in 5 patients, 70/35 in 2 patients, and 70/40 in 2 patients. Toxicities were well tolerated. None of the patients suffered from neurotoxicity or myalgia of more than grade 2. Gastrointestinal disorder was recognized as grade 1-2, and grade 3-4 hematological toxicity included leucocytopenia (64%), anemia (36%), and thrombocytopenia (9%). We set the recommended dose of TXL at 70 mg/m2 and that of CDDP at 35 mg/m2, considering toxicity and performed planned schedule. Of eleven patients, nine were assessable by computed tomographic scan. The overall response rate was 67% (CR: 1, PR: 5, NC: 1, PD: 2). One of two patients with standard TXL/CDDP therapy showed PR by switching to a weekly schedule. The median follow-up duration was 490 days and the median response duration was 371 days. From the results presented here, it is suggested that this regimen with increased DI might be quite effective and well tolerated in patients who experience relapse after CDDP-based chemotherapy.     

Combined action of paclitaxel and cisplatin against wildtype and resistant human ovarian carcinoma cells

Purpose: The combination of paclitaxel (PTX) and cisplatin (DDP) shows good clinical efficacy against ovarian cancer. In order to examine the potential cellular basis for this, and provide leads as to how to optimize the combination, we examined the role of sequence of exposure to PTX and DDP on cell growth in vitro. Methods: Four human ovarian carcinoma cell lines, A121, A2780/WT, A2780/DX5B and A2780/CP3, two human head and neck carcinoma cell lines, A253 and FaDu, and the human ileocecal carcinoma cell line, HCT-8, were treated with PTX + DDP with seven schedules: (A) 96 h exposure to PTX + DDP; (B) 24 h PTX alone, then 72 h PTX + DDP; (C) 4 h DDP alone, then 92 h PTX + DDP; (D) 24 h PTX alone, 4 h DDP alone, then 68 h drug-free; (E) 4 h DDP alone, 24 h PTX alone, then 68 h drug-free; (F) 3 h PTX alone, 1 h DDP alone, then 92 h drug-free; and (G) 1 h DDP alone, 3 h PTX alone, then 92 h drug-free. Each of 66 two-drug experiments included five plates (440 randomly treated wells per experiment). Cell growth was measured by the sulforhodamine B assay. The nature and the intensity of the drug interactions were assessed by fitting a seven-parameter model to data with weighted nonlinear regression, enabling the estimation of an interaction parameter, α, with its standard error. Results: Overall there was very little departure from Loewe additivity: 43 experiments showed Loewe additivity, 10 showed Loewe antagonism, and 13 showed slight Loewe synergy. In vitro Loewe synergy was rare, was small when present, and reproducible only for the A121 and HCT-8 cells exposed to schedule D (24 h PTX prior to 4 h DDP). Isobolographic analysis showed complex combined-action surfaces with regions of local Loewe synergy and antagonism. Conclusion: It appears unlikely that the good clinical efficacy of the combination is primarily caused by a synergistic interaction at the cellular level. Received: 24 October 1996 / Accepted: 5 March 1997     

联合化疗方案治疗晚期胃癌的临床疗效分析和安全性评估

目的探讨联合化疗方案PDF即紫杉醇（PTX）＋顺铂（DDP）＋5-氟尿嘧啶（5-Fu）治疗晚期胃癌的临床疗效情况和安全性。方法入选2008年1月至2010年12月期间晚期胃癌患者80例,随机分为治疗组（40例）和对照组（40例）。对照组患者采用5-Fu治疗。治疗组患者采用PTX（135mg／m^2）静脉滴注3h,第1天;DDP（25mg／m^2）静脉滴注,第1—3天;5-Fu（750mg／m^2）静脉滴注,第1～5天,28天为1个化疗周期。2个周期后分析两组患者的疗效和不良反应。结果治疗组患者中,完全缓解（CR）8例,部分缓解（PR）10例,稳定（SD）15例,进展（PD）7例,临床有效率为45．0％,临床受益率为82．5％,明显高于对照组。治疗组患者的不良反应主要是骨髓抑制和消化道反应,症状较轻,不良反应明显低于对照组。结论采用联合化疗方案治疗晚期胃癌可提高疗效,且不良反应较轻,值得临床上推广。     

Oxaliplatin and paclitaxel combination in patients with platinum-pretreated ovarian carcinoma: An investigator-originated compassionate-use experience

Purpose: Compassionate-use oxaliplatin–paclitaxel was assessed for toxicity and efficacy according to clinical platinum resistance status in cisplatin–carboplatin-pretreated advanced ovarian cancer patients.Patients and methods: Thirty-seven patients, retrospectively grouped into four oxaliplatin–paclitaxel dose levels (mg/m²): (DL1: 100/135; DL2: 130–135/135; DL3: 100/160–175; DL4: 130–135/160–175), received oxaliplatin and paclitaxel every three to four weeks.Results: Thirty-one of thirty-seven treated patients were evaluable for activity, with 1 complete and 14 partial responses, (objective response rate: 48%, 95% CI: 31–66). Of 18 platinum-resistant patients 6 responded, and of 13 platinum-sensitive patients, 9 responded. One patient (3%) had two febrile neutropenia episodes, and eight (22%) and eleven patients (30%) had grades 3 and 4 neutropenia, respectively. Six patients (16%) experienced grade 3 peripheral neuropathy. The median response duration was 10.8 months, with a 23-month (range 8–54) median follow-up. Median progression-free and overall survivals were 9 months (95% CI: 7–12), and 25.2 months (95% CI: 12–39), respectively.Conclusions: The antitumour activity of oxaliplatin–paclitaxel in platinum-resistant ovarian cancer patients accords with experimental data on the agents' lack of cross-resistance. Time-related progression parameters confirm it as a promising salvage treatment option.     

不同剂量紫杉醇静滴联合顺铂腹腔化疗与单纯顺铂腹腔化疗治疗晚期上皮性卵巢癌的疗效与安全性比较

目的:研究紫杉醇不同剂量联合顺铂与单纯顺铂腹腔化疗对晚期上皮性卵巢癌的疗效与安全性差异。方法:选取2013年7月至2016年2月收治的160例晚期上皮性卵巢癌患者,根据紫杉醇给药剂量不同随机分为顺铂组、小剂量组（60 mg/m2）、中剂量组（135 mg/m2）和大剂量组（175 mg/m2）,顺铂给药剂量均为60 mg/m2,每组均40例,3周为1疗程,共6疗程,通过比较各组临床疗效、不良反应发生情况、VEGF、MMP-2、OPN、B7-H4、CA-125指标水平对化疗效果进行评价。结果:小剂量组、中剂量组、大剂量组治疗后OPN、B7-H4、CA-125水平、有效率、疾病控制率均明显的优于顺铂组,差异具有统计学意义（P＜0.05）;高剂量组血小板减少、白细胞减少、恶心呕吐、腹疼腹泻的发生率均显著高于顺铂组及小剂量组,差异具有统计学意义（P＜0.05）;治疗28周后,小剂量组与中剂量组VEGF、MMP-2指标水平比较无明显差异（P＞0.05）,而均优于大剂量组,差异具有统计学意义（P＜0.05）;小剂量组、中剂量组与大剂量组有效率和疾病控制率比较无明显差异（P＞0.05）。结论:晚期上皮性卵巢癌接受紫杉醇联合顺铂腹腔化疗临床疗效较单纯顺铂更加显著,且随着紫杉醇剂量的减少有利于降低不良反应的发生,安全有效,值得临床深入研究。     

Therapeutic effects of the combination of fenretinide and all-trans-retinoic acid and of the two retinoids with cisplatin in a human ovarian carcinoma xenograft and in a cisplatin-resistant sub-line

We previously showed that fenretinide (4-HPR), a synthetic derivative of all-trans retinoic acid (RA), is effective in mice bearing the human ovarian carcinoma IGROV-1 and it significantly enhances the antitumour activity of cisplatin on the same tumour. The present study examined the therapeutic effects of the combination of 4-HPR and RA and of the two retinoids with cisplatin as intracavitary treatments of mice bearing IGROV-1 and IGROV-1/cisplatin tumours, the latter derived from a sub-line with an in vivo reduced sensitivity to cisplatin. 4-HPR, as a single agent, was effective against both tumours, whereas RA had no effect. In IGROV-1 tumour-bearing mice, the combination of RA and 4-HPR significantly improved the efficacy of 4-HPR, resulting in an antitumour activity similar to that obtained with cisplatin alone. N-(4-methoxyphenylretinamide), the main metabolite of 4-HPR, had no antitumour effect and it did not increase 4-HPR activity in IGROV-1 tumour-bearing mice. In the same tumour model, 4-HPR and RA separately increased cisplatin activity, even though for RA the increase was not statistically significant. In contrast, the association of the two retinoids together with cisplatin did not produce any benefit and resulted in increased toxicity. In IGROV-1/cisplatin tumour-bearing mice, the association of 4-HPR (but not of RA) to cisplatin significantly increased cisplatin activity, resulting in the reversal of cisplatin resistance. These findings demonstrate that 4-HPR may be effective and enhance cisplatin sensitivity in cisplatin-sensitive and -resistant ovarian tumours and that the association of RA and 4-HPR may result in increased 4-HPR antitumour activity.     

Midkine as a potential diagnostic marker in epithelial ovarian cancer for cisplatin/paclitaxel combination clinical therapy

The paclitaxel/cisplatin combination therapy commonly is used as the first-line treatment for advanced ovarian cancer patients. Midkine (MK), known as a novel tumor biomarker, has been elevated in the serum of patients with epithelial ovarian cancer (EOC). In this study, we aimed to detect the expression of MK in EOC tissues and evaluate clinical value of MK in diagnosis and therapy of EOC. We perform immunohistochemistry analysis to detect MK in EOC sample with postoperative platinum/paclitaxel combination therapy, we found that 71.4% (85 in 119 samples) of these samples were MK positive (> 10% of the cells were stained), and the expression of MK was significantly associated with disease histology (P = 0.038) as well as differentiation grade (P < 0.001). Moreover, MK positive samples show much more sensitive to cisplatin/paclitaxel combination therapy, compared with MK negative samples (P = 0.029). Those results indicated that MK expression might correlate with paclitaxel and/or cisplatin cytotoxicity in clinical therapy of EOC. Then, we evaluated the sensitivity to cisplatin and paclitaxel in 5 ovarian cancer cell lines (ES2, A2870, HO-8910, SKOV3 and SW626), and ES2, the highest MK expression among those cell lines, show the most sensitive to paclitaxel and cisplatin. Further, we confirmed this correlation between MK and paclitaxel and/or cisplatin cytotoxicity with the gain- and lost- of function. Finally, we demonstrated that MK enhanced the cytotoxicity of paclitaxel and/or cisplatin by accumulated cisplatin and paclitaxel through inhibited the expression of multidrug resistance-associated protein 3 (MRP3). In conclusion, MK could be an effective biomarker in diagnosis and therapy of EOC, especially for the drug selection at the time of initial diagnosis.     

Chemotherapeutic effects of different paclitaxel plus poldine combination methods for treatment of ovarian carcinoma

The study aimed to evaluate the curative effects and toxicity of different paclitaxel (PTX) plus poldine chemotherapeutic combination methods for treatment of advanced ovarian carcinoma. A total of 27 patients with ovarian epithelial carcinoma were divided into four groups: A1, taxotere plus poldine intravenous chemotherapy (n=5); A2, taxotere intravenous chemotherapy combined with poldine intraperitoneal chemotherapy (n=7); B1, paclitaxel plus poldine intravenous chemotherapy (n=6); B2, paclitaxel intravenous chemotherapy combined with poldine intraperitoneal chemotherapy (n=9). Toxic side effects were observed after chemotherapy, and the short-term effects were assessed. Some 25 (25/27) cases completed a four-course treatment, the remaining two stopping halfway due to anaphylactic shock. The total effective rate for the A1 Group was 60% (3/5) and that of A2 group was 71.4% (5/7), Figuires for the B1 and B2 groups were 50% (3/6) and 66.7% (6/9), respectively. In comparisons of toxic side reactions, there were significant differences between taxotere groups and paclitaxel groups, and between intravenous chemotherapy alone groups and intravenous plus intraperitoneal combination chemotherapy groups (p<0.05). Chemotherapy of toxol plus poldine was effective in treatment of advanced ovarian cancer, the toxicities of intravenous plus intraperitoneal combination chemotherapy was lower than that of intravenous chemotherapy alone, and the heart toxicity with taxoere was lower than with paclitexal.     

Pilot study of the paclitaxel, oxaliplatin, and cisplatin combination in patients with advanced/recurrent ovarian cancer

To determine the feasibility of the paclitaxel, oxaliplatin, cisplatin combination in advanced ovarian cancer (AOC), 15 patients with AOC (8 chemonaive, and 7 second-line, disease-free interval > or = 12 months) received paclitaxel 135 mg/m2 at day 1, with oxaliplatin 100 mg/m2 and cisplatin 75 mg/m2 at day 2, every 3 weeks for 6 cycles. Pretreated patients received prophylactic granulocyte colony-stimulating factor (5 microg/kg/d, days 6-13). Seventy cycles were administered; median 5 (range: 2-6 cycles) in chemonaive, and 4 (range: 2-6) in pretreated patients. There were grades III to IV neutropenia in 77%, febrile neutropenia in 24%, and grades III to IV thrombocytopenia in 4% of the cycles. Besides neutropenia, cumulative neurosensory toxicity was also limiting although reversible, with National Cancer Institute Common Toxicity Criteria grades II to III observed in 13 patients. Three of the pretreated patients had complete responses (43%), three had partial responses, and one had disease stabilization. Six of the 8 chemonaive patients had complete responses (75%), 1 had disease stabilization, and 1 had disease progression. The median follow-up is 17 months (range: 9-20 months) in chemonaive and 41 months (range: 13-58 months) in pretreated patients, and time to progression has been consistently more than 12 months, with 6 patients (5 chemonaive) still progression free (range: 15+ to 22+ months).This active combination shows acceptable hematologic toxicity, and reversible cumulative neurosensory toxicity. Further clinical exploration of the present combination appears warranted.     

Treatment of advanced and recurrent ovarian carcinoma with cyclophosphamide, doxorubicin, and cisplatin

Forty-seven patients with primary advanced (N = 37) or recurrent ovarian carcinoma (N = 10) completed a 12-month course of CAP chemotherapy or developed progressive disease while on therapy and were evaluated. All patients were treated between August 1, 1977 and August 1, 1982. Cyclophosphamide 400 mg/m2, Adriamycin (doxorubicin) 40 mg/m2, and cisplatin 60 mg/m2, were administered every 4 weeks intravenously. After 8 courses the cisplatin was stopped. The patients then received 500 mg/m2 of cyclophosphamide and 50 mg/m2 of Adriamycin. At the cumulative dose of 450 mg/m2, the Adriamycin was stopped and cyclophosphamide was given at 1 g/m2 alone until the patient had received a total of 12-13 courses from the initiation of the chemotherapy protocol. The cardiac, renal, and hematopoetic toxicity of the regimen was mild to moderate. The median survival of the entire study population was 32 months. The median survival of the patients with primary disease was 36 months. The median survival of patients with recurrent disease was 20 months. There was a significant difference in median survival based on size of the largest lesion prior to initiation of chemotherapy. There was no difference in median survival based on tumor grade or comparing Stage III to Stage IV tumors. The most important aspects of the study appeared to be the length of the median survival of the patients, the fact that all patients who were complete responders and who were considered to have no evidence of disease, have been documented by second look, and the success of secondary treatment after second-look procedures revealed persistent tumor. The authors additionally report the use of weight change as an indicator of tumor response, and the importance of the pelvic examination complimented by fine-needle aspiration in following the course of these patients.     

Cytotoxicity of paclitaxel in combination with cisplatin and a new Pt-mercaptopyridine complex

In vitro synergy has been reported for exposure to paclitaxel prior to cis-platin (cis-DDP), whereas the reverse sequence resulted in antagonism. There is no clear evidence for an intracellular origin of the schedule-dependent interaction, but several hypotheses have been proposed, such as effects at the level of DNA crosslinks, or binding to tubulin sites. The purpose of this study was to evaluate the cytotoxicity of these two drugs as single agents, in combination and in sequence, against a human colon adenocarcinoma cell line (LoVo). Moreover, we considered the new Pt-mercaptopyridine complex C/2, was like cis-platin in being able to alter DNA conformation. We have therefore studied the cytotoxic effects after single agent exposure, concomitant exposure (paclitaxel + cis-platin and paclitaxel + C/2) and sequential drugs exposure (paclitaxel-->cis-platin and cis-platin-->paclitaxel or paclitaxel-->C/2 and C/2-->paclitaxel). Our results demonstrate that the most cytotoxic effect is induced by paclitaxel and C/2 exposure both in the case of concomitant cell treatment and sequential exposure paclitaxel-->C/2.     

The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in paclitaxel combination chemotherapy for epithelial ovarian carcinoma

Shakuyaku-Kanzo-to was first medicated for muscular pain which was called Komuragaeri, and it has been reported that it is effective for peripheral nerve dysfunction such as arthralgia and numbness. Recently, Paclitaxel (T) and Carboplatin (J) combination chemotherapy (TJ chemotherapy) has been a standard first-line chemotherapy for epithelial ovarian carcinoma. For the arthralgia and muscular pain occurring in TJ chemotherapy, non-steroid-anti-inflammatory drugs (NSAIDs), Vitamin B12 (VB12) and Shakuyaku-Kanzo-to are the major medications. In this study, we examined twenty-one cases in which arthralgia and muscular pain occurred in TJ chemotherapy (including 16 cases as first-line chemotherapy). In all cases, patients took 7.5 g of Shakuyaku-Kanzo-to orally per day for eight days. We investigated the efficacy of Shakuyaku-Kanzo-to retrospectively with the following results. In nine cases (43%), Shakuyaku-Kanzo-to was effective in reducing pain. Especially in TJ chemotherapy as first-line chemotherapy, Shakuyaku-Kanzo-to was even more effective in reducing pain. We suggested that Paclitaxel combination chemotherapy with Shakuyaku-Kanzo-to taken orally is a more safe and tolerable way to reduce pain in epithelial ovarian carcinoma.     

High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma

Background: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin–paclitaxel.Design: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients.Patients and methods: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m² followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg·ml^-1·min.Results: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%–54%). Response rates for platinum-refractory patients and those with early (3 and <12 months) and late (>12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy.Conclusion: This combined paclitaxel–carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.