DNA ploidy and S-phase measurements were made in fresh tumour samples obtained from 27 patients with either untreated or previously treated ovarian cancer. In addition, an assessment of in vitro chemosensitivity to post-operative chemotherapy was carried out. Whilst we found that patients with aneuploid tumours tended to survive longer (median survival 441 days versus 268 days for diploid tumours; p = 0.308) and this was associated with clinical response (p = 0.137) this was not statistically significant. Tumours with a high S-phase fraction (i.e. > 9% median) showed a median survival of 362 days compared with 484 days for those with a low S-phase fraction (< 9%; p = 0.79). Whilst a high level of predictability for chemosensitive patients (81%) was achieved, chemosensitivity per se was not related to the respective tumour DNA ploidy or S-phase fraction. In addition, when considering disease stage i.e. FIGO stage III or IV, or extent of residual disease between diploid and aneuploid groups, there were no statistically significant differences. However, there was a tendency for stage III tumours to be aneuploid (p = 0.189). Aneuploid tumours also showed the highest S-phase fractions (p = 0.03), indicative of a high proliferation rate. In conclusion, we have shown that DNA content and ploidy status do not appear to be major prognostic indicators for the management of ovarian cancer.

Adult↗

PubMedDate not supplied

In vitro sensitivity to the liposomal preparation, DaunoXome in CLL.

In order to determine the efficacy of liposomal encapsulated daunorubicin (DaunoXome; DNX) in chronic Iymphocytic leukaemia, the sensitivities of cells from 10 patients with this disease were assessed and compared with that of free drug using the MTT assay. There was a marked variation in effect between patients for both drug preparations. Despite this, there was a small but significant enhancement of cytotoxicity afforded by the liposomal preparation (median 2.8-fold, p < 0.01). The cells from 2 of the patients appeared to be resistant to free daunorubicin. However, incubation for 96 h in DNX appeared to circumvent this resistance. This increase in sensitivity for resistant cells could not be demonstrated in an MDR positive cell line (K562AR) suggesting that another mechanism of resistance may be involved. We conclude that it is feasible to assess sensitivity to DNX using the MTT assay in fresh cells from patients with CLL using a continuous drug exposure of 96 h. Furthermore, DNX appears more effective than free drug in this disease.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

The activity of N-(hydroxymethyl) melamines in fresh human ovarian tumour cells and xenografts.

Trimelamol (TM) was developed as a water soluble analogue of the oral chemotherapeutic agent hexamethyl-melamine (HMM), to be administered i.v., in an effort to avoid dose limiting emesis. Because of formulation difficulties due to its inherent instability the development of TM was halted. In vivo studies using a human ovarian cancer xenograft model PXN/65 showed TM to be curative in the dose range of 15-60 mg/kg i.p. daily x 5, for 4 weeks. Conversely, HMM given at the highest dose (60 mg/kg i.p., or 90 mg/kg p.o.) indicated only very modest tumour growth delays. In vitro chemosensitivity testing using primary ovarian tumour cultures showed that in 12/23 cases indicating reduced sensitivity to cisplatin or carboplatin, sensitivity to TM was increased. TM was curative in the carboplatin-resistant HX 110P human ovarian cancer xenograft and promising activity was seen in the MX-1 human breast cancer xenograft. In spite of enhanced stability in aqueous solution and good in vitro cytotoxicity, the TM analogues CB 7669 (triscyanomethyl) and CB 7639 (tristrifluoroethyl) showed disappointing in vivo antitumour activity which may be explained by the need for prolonged exposure. TM analogues with intermediate stability are currently under development in an effort to further the clinical development of this promising group of antitumour agents.

Altretamine↗