Impairment of heart rate variability during paclitaxel therapy.

BACKGROUND: Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. METHODS: Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005-0.040 hertz [Hz]), low (0.040-0.150 Hz), and high frequency (0.150-0.400 Hz) spectral components. RESULTS: The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.91; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. CONCLUSIONS: The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy.

PAP smear after radiation therapy for cervical carcinoma.

Vaginal PAP smear is frequently used for the follow-up of cervical carcinoma after primary therapy. Irradiation induced atypia can interfere with cytological analysis and thus detection of a local recurrence, or simulate malignant atypia and cause unnecessary suspicion of recurrence. In this retrospective study we evaluated the reliability of cytological analysis and the reported frequency of irradiation induced atypia after radiotherapy. Eighty-nine patients treated for cervical carcinoma at Turku University Central Hospital during the years 1970-88 were included in the study. During the median follow-up of 34 months a total of 697 PAP smears were taken with a median of 7.8 samples per patient. During the follow-up 44 (50%) patients had a recurrent disease, which was local in 17 (39%) cases. Nine out of 12 PAP smears taken 0-60 days before detection of a local recurrence showed class III-V cellular atypia. However, three PAP smears showed class I-II, and were therefore false negative. The rate of false positive samples was only 3%. In 567 PAP smears irradiation induced atypia was indicated as present/not present (+/-) and it was positive in 89 (16%) samples. The detection rate was considerably higher (75%) in class II samples than in rest of the material. Irradiation induced atypia was detected in 28% of the PAP smears taken during the first four months after radiotherapy and the rate decreased thereafter. Cytological analysis of vaginal PAP smear was a reliable indicator of recurrence in most cases and is a valuable tool for the detection of local recurrence of cervical carcinoma after primary radiotherapy.

High-dose chemotherapy with autologous stem cell support in advanced ovarian cancer.

Since 1981, over 300 patients reported with advanced or refractory ovarian cancer have been treated with high-dose chemotherapy supported by autologous bone marrow or peripheral blood stem cell transplantation. Partial or complete clinical response has been reported in 54-100% of the cases, but the median duration of the response in the majority of patients has been only a few months. It is obvious from the available data that high-dose regimens supported by autologous stem cell transplantation (ASCT) are not capable of inducing long-term survival in patients with heavy tumour burden or chemoresistant ovarian cancer. Recent reports on nearly 100 patients have described results of the use of high-dose chemotherapy as first-line treatment for patients with optimally debulked disease or negative second-look laparotomy. Response rates and survival have been better when compared to historical controls, but the efficacy of this treatment modality in inducing durable remission has not been tested in randomized trials. Most of the ongoing trials presented briefly in this review have been designed to evaluate the potential of high-dose therapy as first-line treatment in preventing the development of resistant tumour clones and recurrence. The role of sequential high-dose chemotherapy with ASCT as a part of primary treatment or as salvage therapy for chemosensitive recurrent disease is also under investigation.

The role of cul-de-sac aspiration cytology in the follow-up of ovarian cancer.

The methods most often used for follow-up of ovarian cancer are physical examination, CA-125 measurement and ultrasonography or computed tomography. In the present study the role of cul-de-sac aspiration cytology as a supplementary method was evaluated. We analyzed the records of 110 stage I-IV ovarian cancer patients who had undergone cul-de-sac aspiration as a part of their follow-up schedule after the primary treatment. During the median follow-up of 5 years altogether 577 cul-de-sac aspirations were performed with a median interval of 9 months. Only in 2 cases the obtained sample was insufficient for evaluation. Twenty patients had cul-de-sac cytology > or = class III at some point during the follow-up. In 12 cases the preceding or subsequent CA-125 values taken within 3 months were < 35 U/l. In 7 cases CA-125 values increased later, but in 5 cases the tumour marker values remained within normal range during the entire follow-up. Nine out of these 12 patients had a clinical recurrence later on, but 3 patients had no evidence of the disease. Twenty-seven recurrences were detected during the follow-up. Cul-de-sac aspiration cytology was the first or the only indication of recurrence in 9 cases (33%) and is a useful supplementary method in the follow-up of ovarian cancer.