Neoadjuvant chemotherapy with cisplatin, aclacinomycin A, and mitomycin C for cervical adenocarcinoma – a preliminary study

Between 1989 and 2002, 28 patients with locally advanced cervical adenocarcinoma (bulky IB-IIIB) were recruited for a pilot study aimed at evaluation of the effectiveness of neoadjuvant chemotherapy with cisplatin, aclacinomycin-A, and mitomycin-C (PAM), followed by radical surgery. This regimen was administrated intra-arterially or intravenously. In addition to patients treated with PAM, we retrospectively analyzed the prognoses of 26 patients in stage I and II, who had been treated between 1975 and 1981 with radical surgery with/without radiation therapy. Twenty-eight patients received PAM therapy as neoadjuvant chemotherapy, and 75.0% of the 16 intra-arterially infused patients showed a response, as did 66.7% of the 12 intravenously infused patients. There was a significant difference in the 5-year prognosis of stage II (PAM group, 72.9%; without-PAM group, 36.4%). The results suggest that, as the free space in the parametrium is widened by neoadjuvant chemotherapy with PAM, it is possible that the tumor could be completely resected by radical hysterectomy. Thus, neoadjuvant chemotherapy with PAM is expected to improve the survival rate of patients with advanced cervical adenocarcinoma by the preliminary study. However, the survival rates of stage II with lymph node metastasis in the without-PAM group seem low, and we must also consider that the various technologies to evaluate and treat the cervical adenocarcinomas, e.g. computed tomography, magnetic resonance imaging, and surgical equipments, had improved during 1989-2002 than was the scenario during 1975-1981, and these improvements contributed to better prognosis. A prospective-randomized study is needed to assess the value of this approach compared with standard management.     

Placental site trophoblastic tumor in a patient with brain and lung metastases

Placental site trophoblastic tumor is a rare neoplasm that arises from intermediate trophoblasts and shows diversity of biological behaviors, resulting in the absence of consistency in treatment modalities. A case of placental site trophoblastic tumor that extended to the cervix, with primary manifestation of amenorrhea and yellow foul-smelling vaginal discharge, is presented. Total abdominal hysterectomy was performed initially, and serial measurements of human chorionic gonadotropin levels were obtained. She was admitted with metastases to brain and lung 1.5 years after surgery. Combination chemotherapy (etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine) and radiotherapy were administered. There was no significant response to chemoradiotherapy. Despite changing chemotherapy regimen, she is still alive with progressive disease.     

下咽癌120例临床疗效的回顾性分析

目的探讨下咽癌单纯手术、术后放疗和术后放疗 化疗的临床疗效。方法回顾性分析1979年2月~2002年10月收治的下咽癌120例。单纯手术组(简称S组)30例,术后放疗组(简称S R组)60例,术后放疗和化疗组(简称S R C组)30例。随访中位时间42.7个月。结果根据Kaplan-Meier方法统计S组、S R组、S R C组3、5年生存率分别为34.9%、30.4%,47.5%、42.9%,56.1%、47.3%。S组3、5年生存率和S R组及S R C组3、5年生存率存在显著性差异(χ2=8.87,P=0.003,χ2=4.74,P=0.029,χ2=11.47,P=0.009,χ2=13.22,P=0.001),S R组和S R C组3年生存率存在显著性差异(χ2=3.42,P=0.047),S R组和S R C组5年生存率差异无显著性(χ2=2.60,P=0.279)。结论术后放疗明显提高了下咽癌3、5年生存率,应该成为下咽癌首选的治疗方法。合并化疗的综合治疗未能明显提高下咽癌5年生存率。     

Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

BACKGROUND: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. PATIENTS AND METHODS: Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. RESULTS: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). CONCLUSIONS: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.     

Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.

BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.     

Chemotherapy-induced amenorrhea: influence on disease-free survival and overall survival in receptor-positive premenopausal early breast cancer patients.

BACKGROUND: The aim of this study was to evaluate the influence of early chemotherapy-induced amenorrhea (CIA) on disease-free survival and overall survival in premenopausal patients with receptor-positive early breast cancer treated with adjuvant chemotherapy without any hormonotherapy. PATIENTS AND METHODS: Retrospectively, we reviewed data from 130 premenopausal patients with localized hormone-sensitive breast cancer. These patients were treated between 1985 and 1995 at the same institution. They all underwent a loco-regional treatment and adjuvant chemotherapy. Early CIA was defined as an amenorrhea arising during the first year following the beginning of chemotherapy. Predictors of early CIA were examined. The survival analyses were done using the Kaplan-Meier method and Cox analysis. RESULTS: Median follow-up was 9 years. Mean age was 42.9 +/- 5 years. Ninety-two per cent of patients had histologically-proven positive axillary nodes. Adjuvant chemotherapy contained no anthracycline in 63%. Early CIA occurred during or after adjuvant chemotherapy in 57% of the patients. It was definitive in 91%. In our study, age was the only CIA predictor in univariate analysis. Women who experienced early CIA tend to have a longer disease-free survival, but the difference was not significant. This trend was lost in multivariate analysis, most probably due to the small sample size. The overall survival was not different. CONCLUSION: Although not statistically significant, our results on a very selected population of patients suggest that a chemotherapy-induced amenorrhea might have its own therapeutic effect besides the cytotoxic action of chemotherapy.     

MRI and conservative treatment of locally advanced breast cancer

AIMS: The objectives of this study were to compare the efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the response of primary breast carcinoma to neoadjuvant chemotherapy compared to conventional imaging modalities, and to see how surgical outcome was influenced as a result of these findings. METHODS: Thirty-four patients with locally advanced primary breast cancer underwent conventional imaging and DCE-MRI following six cycles of neoadjuvant chemotherapy prior to surgery. Changes in surgical management based on the post-chemotherapy DCE-MRI findings were recorded. RESULTS: Prior to neoadjuvant chemotherapy, 22 of the 34 patients were assessed as requiring mastectomy and the remaining 12 were considered inoperable. Following chemotherapy two patients were still considered inoperable. In 11 of the 34 patients, the final decision to proceed to either mastectomy or non-surgical management was based primarily on pre-treatment disease status or patient choice. DCE-MRI findings, therefore, contributed to the operative decision in 21 of 34 patients. Two of these 21 patients were spared surgery as DCE-MRI demonstrated complete response to chemotherapy and one declined surgery. The remaining 18 were able to undergo wide local excision, with only two patients subsequently requiring mastectomy for involved margins. CONCLUSIONS: DCE-MRI is able to accurately predict those patients suitable for breast conserving surgery following neoadjuvant chemotherapy and should be the imaging modality of choice in assessing the response of patients with primary breast carcinoma to neoadjuvant chemotherapy.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.