Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis

Poor outcome of treatment in advanced cervix carcinoma has been shown to be associated with poor oxygenation of the primary tumour. Hypoxia may cause radiation resistance and promote lymph-node metastasis. The purpose of the study reported here was to investigate whether hypoxia-induced treatment failure in advanced cervix carcinoma is primarily a result of hypoxia-induced radiation resistance or the presence of hypoxia-induced lymph-node metastases at the start of treatment. Thirty-two patients with squamous cell carcinoma of the uterine cervix were included in the study. Radiation therapy was given with curative intent as combined external irradiation and endocavitary brachytherapy. The oxygenation status of the primary tumour was measured prior to treatment using the Eppendorf p O 2 Histograph. Pelvic and para-aortal lymph-node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. The primary tumours of the patients with metastases (n = 18) were significantly more poorly oxygenated than those of the patients without metastases (n = 14). Multivariate Cox regression analyses involving biological and clinical parameters identified the tumour subvolume having p O 2 values below 5mmHg (HSV (p O 2< 5mmHg) as the only significant, independent prognostic factor for locoregional control, disease-free survival and overall survival. The probabillities of locoregional control, disease-free survival and overall survival were significantly lower for the patients with HSV (p O 2< 5 mmHg) above the median value than for those with HSV (p O 2< 5 mmHg) below the median value. On the other hand, the outcome of treatment was not significantly different for the patients with metastases and the patients without metastases at the start of treatment, irrespective of clinical end-point. Consequently, treatment failure was primarily a result of hypoxia-induced radiation resistance rather than hypoxia-induced lymph-node metastasis, suggesting that novel treatment strategies aiming at improving tumour oxygenation or enhancing the radiation sensitivity of hypoxic tumour cells may prove beneficial in attempts to improve the radiation therapy of advanced cervix carcinoma. © 2000 Cancer Research Campaig

Weekly cisplatin and daily oral etoposide is highly effective in platinum pretreated ovarian cancer

We investigated the potential of weekly cisplatin and daily oral etoposide followed by oral etoposide maintenance therapy in patients with platinum-refractory ovarium cancer. One hundred and seven patients were entered on the study, 98 patients completed the induction therapy consisting of cisplatin at either 50 or 70 mg m−2 weekly for six administrations plus oral etoposide at a dose of 50 mg daily. Of these 98 patients, 38 had a platinum treatment-free interval of more than 12 months, 32 had an interval between 4 and 12 months, and 28 had progressed during or within 4 months after last platinum therapy. We assessed response rates and time to progression, and also response duration and survival. Analyses were done on the 98 evaluable patients. All 107 patients were considered evaluable for toxicity. Of the 38 patients with a treatment-free interval of more than 12 months, 92% responded, with 63% complete responses. The median progression-free survival in these patients was 14 months, and the median survival was 26 months. Of the 32 patients with an interval of 4–12 months, 91% responded, with 31% complete responses, a median progression-free interval of 8 and a median overall survival of 16 months. Of the 28 patients with platinum-refractory disease, 46% as yet responded, with 29% complete responses, median progression-free interval of 5 and an overall survival of 13 months. Haematologic and non-haematologic, particularly renal toxicity and neurotoxicity, were notably mild. We conclude that this intensive regimen of weekly cisplatin plus daily etoposide is highly effective and well tolerated in patients with ovarian cancer relapsing after conventional platinum-based combination chemotherapy, including patients who have progressed during or within 4 months after platinum treatment

Morbidity associated with "self-rated health" in epithelial ovarian cancer survivors

<p>Abstract</p> <p>Background</p> <p>Epithelial ovarian cancer survivors (EOCSs) frequently report multiple complaints after their treatment. The objective was to study somatic and mental morbidity in EOCSs associated with their Self- Rated Health (SRH) assessed by a single item.</p> <p>Findings were compared to age-matched controls from the general population.</p> <p>Methods</p> <p>In a cross -sectional follow-up design 189/287 (66%) EOCSs treated at The Norwegian Radiumhospital 1979–2003 responded to a mailed questionnaire on demographic data, and somatic and mental morbidity. SRH last week was rated on item #29 of the European Organization and Treatment of Cancer Quality of Life Questionnaire in 84/189 (97%) of responding EOCSs. For comparisons "good" and "poor" SRH groups were defined by the median score on the SRH item.</p> <p>Results</p> <p>EOCSs with "poor SRH" had higher level of somatic symptoms, anxiety, depression and fatigue than those with "good SRH" (p < .001). In multivariate analyses somatic symptoms, age and fatigue, were significantly associated with the SRH score in EOCSs, but not the cancer-related variables (FIGO stage, recurrence in < 6 months or chemotherapy ever). The model explained 70% of the variance in SRH in linear and 77% in logistic regression analyses. The distribution of the SRH scores in EOCSs did not differ significantly from that of normative controls; however a higher proportion of controls recorded a high SRH score.</p> <p>Conclusion</p> <p>SRH is strongly related to common somatic complaints, impairment and fatigue but not to cancer-related variables. A single question concerning SRH last week might be a quick screening method for collecting important information on symptoms in EOCSs, in addition to cancer – related questions.</p