Antiemetic treatment of chemotherapy-induced nausea in ovarian carcinoma patients

In a prospective, randomized, double-blind trial the combination betamethasone-dixyrazine was compared with high-dose metoclopramide as antiemetic treatment during combination chemotherapy (melphalan-doxorubicin and cisplatin) of ovarian carcinoma. Of 40 evaluable patients, 15 (38%) had previous experience with chemotherapy. Efficacy and side effects were recorded on patient and nurse questionnaires using the visual analog scale. Nausea and vomiting were prevented in 55% of the patients treated with melphalan-doxorubicin (Day 1) and in 36% of the patients treated with cisplatin (Day 2). Betamethasone-dixyrazine was superior to high-dose metoclopramide and prevented nausea in 76% compared to 32% during melphalan-doxorubicin therapy. Akathisia was noted in 21% and acute dystonic reactions in 2.6% during metoclopramide treatment but not in any case during betamethasone-dixyrazine therapy.     

The effect of metoclopramide, dexamethasone and antihistamine in the prevention of PAC chemotherapy-induced emesis

The effect of antiemetic agents on the nausea and emesis of ovarian cancer patients treated with CDDP (45 mg/m2), ADM (45 mg/m2) and CPM (450 mg/m2) combination chemotherapy was examined in a randomized parallel study. Metoclopramide (1 mg/kg, 4 times every 2.5 hours), dexamethasone (3.8 mg, 4 times every 2.5 hours) and antihistamine (10 mg, 2 times every 5 hours) were used as antiemetic agents and these agents were gradually decreased for 5 days. The above regimen significantly suppressed the frequency and volume of vomiting on the day of the first PAC chemotherapy but showed no effect on the delayed persistent nausea during chemotherapy. The frequency and volume of vomiting on the day of chemotherapy were 1.6 times and 102 ml respectively in the antiemetic group, but 8.9 times and 352 ml, respectively, in the control group. Although this antiemetic regimen sufficiently suppressed acute drug-induced emesis during chemotherapy, delayed persistent nausea was not eliminated. We next investigated whether these combined antiemetic agents protected the quality of life of patients during maintenance chemotherapy. Our data indicated that about 2 weeks was necessary to recover health after maintenance PAC chemotherapy. These results indicated that this regimen was effective in suppressing the acute drug-induced emesis and in maintaining the quality of life following maintenance PAC chemotherapy.     

Antiemetic efficacy of high-dose metoclopramide, diphenhydramine, methylprednisolone and diazepam on chemotherapy-induced emesis in gynecological malignancy

The antiemetic efficacy of high-dose metoclopramide (MCP), diphenhydramine (DPH), methylprednisolone (MPL), and diazepam (DZP) was investigated in 40 gynecologic cancer patients for a total of 98 chemotherapy courses, treated with cisplatin (50 mg/m2). With MPL (500 mg i.v. x 2) plus DZP (5 mg i.m. x 2), no vomiting occurred in 0% and mild emesis (vomiting 1-2 times) occurred in 20% of 25 courses. With MCP (2 mg/kg i.v. x 5) plus DPH (40 mg i.v. x 3), no vomiting occurred in 35% and mild emesis occurred in 10% of 20 courses. With a combination of MCP plus DPH and MPL plus DZP, no vomiting occurred in 51% and mild emesis occurred in 25% of 53 courses. These results indicate that high-dose MCP plus DPH are effective in preventing cisplatin-induced vomiting. Furthermore, the antiemetic efficacy of MCP plus DPH (0-2 vomiting episodes: 45%) was significantly enhanced (p less than 0.05) by the combined use of MPL plus DZP (0-2 vomiting episodes: 76%).     

Treatment of advanced ovarian cancer with cisplatin, adriamycin and cyclophosphamide (PAC)

Forty two ovarian cancer patients with residual disease after the first laparotomy were treated with the combination of cisplatin (80 mg/m2 day 1), adriamycin (50 mg/m2 i.v. day 2) and cyclophosphamide (500 mg/m2 i.v. day 2) (PAC). Forty women were considered evaluable for analysis, with an overall response rate (partial, plus complete responses) of 62.5%. Twelve patients (30%) obtained a complete response (histologically confirmed after second look surgery in 6 cases, surgical complete response, residual tumor completely resected in the second look-in 5 cases and maintained complete clinical remission without second look confirmation in 1 case). Main side effects were nausea and vomiting (90%), leukopenia (70%), mucositis (45%), and anemia (37%). Seventeen percent of the patients were free of disease at 60 months, after a median follow-up of 48 months. The prognostic factors that showed significant influence on survival were the Karnofski index (90-100 vs 80 or less), stage of the disease (II + III vs IV) and the volume of residual tumor after the first surgical procedure (less than or equal to 2 cms vs greater than 2 cms). Patients who achieved a complete remission have not reached the median 5 years survival, which was 10 months for the remaining patients. These results confirm the activity of PAC in ovarian cancer, mainly in those patients with residual tumor of less than 2 cms and good performance status.     

Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity

Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.     

Short-duration (three cycles) cisplatin combination chemotherapy with alkylating agent consolidation in advanced epithelial ovarian cancer

Forty-eight patients with advanced epithelial ovarian cancer were treated with a two-part cytotoxic regimen consisting of three cycles of cisplatin-based induction therapy followed by five cycles of escalating doses of cyclophosphamide, all given at 3-weekly intervals. The total cisplatin dose was 225 mg/m2. Seventeen patients with optimal primary surgery received chemotherapy only, while 17 of the 31 patients with suboptimal primary surgery underwent optimal interval cytoreductive surgery at the end of induction (cisplatin) therapy. Median survival for all patients was 15.4 months. Median survival was 15 months for patients with optimal primary surgery and 22 months for patients who had optimal secondary cytoreduction. Only 10 patients suffered WHO grade 3 or greater toxicity during therapy. This study suggests that the total dose of cisplatin can be reduced for patients with advanced ovarian carcinoma, resulting in reduced overall toxicity, without compromising response or response duration. A randomized trial to test this concept is now underway.     

Tumor marker combination versus second-look operation in ovarian cancer

Tumour markers are substances that occur at elevated blood levels in patients with certain tumours. When their specificity and sensitivity are known, markers can be used to monitor cancer patients. No single marker is specific and sensitive for a certain tumour, so a tumour-marker combination is used. The efficacy of CA 125, ferritin, TPA and CEA was demonstrated in 162 ovarian cancer patients. With the same combination, we found a statistically significant 91.7% correlation between the clinical course of the disease and the marker profile in 60 further patients. Tumour markers can also help make a prognosis. In 34 patients the marker profile accurately predicated the findings at second-look surgery. Thus, biochemical monitoring may supplant the second-look procedure. 68 patients were followed for a mean of 2.7 years after completion of chemotherapy. In 95.6% the tumour-marker analysis correlated with the clinical and radiologic course. This means that the end of chemotherapy depends on biochemical monitoring, and second-line therapy can be initiated sooner.     

The study of cyclic maintenance chemotherapy with cisplatin, adriamycin, and cyclophosphamide (cyclic PAC chemotherapy) in patients with advanced ovarian cancer

The efficacy of two methods of chemotherapy in the treatment of patients with advanced ovarian cancer was compared on the basis of survival curves; one consisted of remission induction therapy alone with a combination of cisplatin (CDDP), adriamycin (ADM) and cyclophosphamide (CPM) (induction PAC therapy), and the other consisted of induction PAC therapy and additional maintenance therapy with cyclic PAC (cyclic PAC therapy). The subjects of the study were patients with advanced ovarian cancer in stages III and IV. Sixty-eight patients received induction PAC therapy alone and seventeen patients received both induction and cyclic PAC therapy. Demographic factors such as age at initial presentation, the stage of cancer (III or IV), surgical procedure, histological classification, number of courses of induction PAC, response rate, site of residual tumor after surgery and induction PAC therapy, and reduction rate of CA125 were compared in the two groups. When analyzed by the chi 2 test, none of these factors was significantly different in the two groups. Patients in the induction PAC therapy group received a median total dosage of CDDP 360 mg, ADM 235mg, and CPM 2.246mg. Patients in the cyclic PAC therapy group received CDDP 592mg, ADM 490mg, and CPM 4.642mg. Thus, the dosage of anticancer agents administered to the latter group was about twice as great as that administered to the former group. According to the Kaplan-Meier method, survival rates for the induction PAC therapy group were 88.2% for one year, 50.0% for two years, 28.0% for three years, and 8.8% for five years. The median survival period was 23 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carboplatin and chlorambucil combination chemotherapy as treatment for patients with ovarian cancer

Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage III and II stage IV) were treated with carboplatin 350 mg m⁻² i.v. day 1 and chlorambucil orally 0.15 mg kgm⁻¹ days 1–7 inclusive, repeated every 28 days for eight courses. The regimen was well tolerated and was virtually free of nephro- and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients but only 31 or 330 courses administered were delayed. Of 40 assessable patients eight achieved a clinical/radiologic complete response and 17 a clinical/radiologic partial response. Actuarial survival at 50 months was 65% for stage II patients, 27% for stage III patients and no stage IV patients survived beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm survived 50 months, compared with 44% of patients with moderate volume (2–5 cm) residual disease and 6% of patients with bulk residual disease. This is an active, well tolerated regimen. However, only patients with small volume residual disease have a significant chance of prolonged survival.     

Antiemetic efficacy of high-dose corticosteroids and droperidol in cisplatin-induced emesis: A controlled trial with droperidol and metoclopramide

The nausea and vomiting associated with cisplatin chemotherapy make care of the patient more difficult for nurses and physicians, can cause severe metabolic and pathologic sequelae, and preclude further courses of chemotherapy. Current reports suggest that the two most efficacious agents for antiemetic prophylaxis are metoclopramide and corticosteroids. These two agents in combination with droperidol have been compared in a randomized controlled prospective fashion. Patients had less nausea and vomiting on the steroidal regimen than the nonsteroidal regimen (P less than 0.05), and the duration of nausea and vomiting was significantly less on the steroidal regimen (P less than 0.05). Patients expressed a preference for the steroidal regimen over the nonsteroidal one and the steroidal regimen retained its antiemetic effectiveness through repeated courses of chemotherapy. The results of the study suggest that corticosteroids and droperidol are superior antiemetic agents for cisplatin-induced nausea and vomiting.     

NCCN《2012卵巢癌包括输卵管癌和原发腹膜癌临床实践指南第２版》解读

最近,美国国立综合癌症网络(National Comprehensive Cancer Network,NCCN)公布了《2012卵巢癌包括输卵管癌和原发腹膜癌临床实践指南第2版》。现对新版指南进行简要解读。1上皮性卵巢癌     

Cisplatin, methotrexate, and 5-fluorouracil combination chemotherapy for advanced ovarian cancer

A combination chemotherapy including cisplatin, 25 mg/m2 on Days 1,8; methotrexate, 30 mg/m2 on Day 1; and 5-fluorouracil, 600 mg/m2 on Day 1 has been evaluated in 28 previously untreated and 10 pretreated patients with advanced ovarian cancer after debulking surgery when feasible. The pathological response rates (complete + partial responses) were 69.2 and 50% in untreated and pretreated patients, respectively. Overall 24-month survival and progression-free survival (PFS) are 19.2 and 10.9%, respectively. A significant difference in survival and PFS is evident between patients with less and more than 2 cm residual disease and between responders (CR + PR) versus nonresponders. No renal toxicity was induced and no cycles had to be delayed because of hemathologic toxicity.     

Salvage chemotherapy for ovarian cancer recurrence: weekly cisplatin in combination with epirubicin or etoposide

From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.     

Estrogen receptors (ER) and progesterone receptors (PgR) in ovarian cancer]

The paper reviews recent advances regarding interactions between cells and steroid hormones together with the latest data on receptor content in normal and malignant ovarian tissue and their importance in tumoral biology. Three recently published studies confirm that there is an 84% concentration of PgR and 35% of ER in the normal ovary. The incidence of steroid receptors in benign tumours is virtually the same as that found in normal tissue, except for a slight increase in PgR, whereas in malignant ovarian cancer ER and PgR receptors show marked changes. PgR levels fall dramatically from 94% to 42%, while there is a slight rise in ER levels. It has also been demonstrated that low receptor status tumours were more aggressive than those with high receptor positivity in all patients with a follow-up of two or more years. In terms of clinical management, the tumour differences led to the use of synchronised chemohormonal treatment. Preliminary data are encouraging but further research is required to identify the optimal combination. With reference to receptor expression in relation to prognosis it appears clear that receptor-positive tumours have a better prognosis than receptor-negative ones.