Docetaxel and cisplatin in combination as first-line chemotherapy for advanced epithelial ovarian cancer. Scottish Gynaecological Cancer Trials Group.

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel 75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and docetaxel 85 mg/m(2)). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m(2) adds unacceptable hematologic toxicity and potential risks to the patient.

Population-based p16 and HPV positivity rates in oropharyngeal cancer in Southeast Scotland.

We assessed a population-based cohort of patients diagnosed with oropharyngeal squamous cell carcinoma in Southeast Scotland over 13 months. p16 and human papilloma virus (HPV) expression were determined, and correlated with stage, treatment, smoking and alcohol history, and disease outcomes. Retrospective analysis was performed on 60 patients. p16 immunohistochemistry and HPV genotyping were performed on formalin-fixed paraffin-embedded tissues. HPV infection (as defined by p16 positivity and/or HPV PCR positivity) was identified in 57% of samples, while dual positives were detected in 45% of cases. HPV16 was most prevalent of the HPV types and was associated with 90% of positive samples. Cause-specific 1-year and 2-year survivals were 82.5% and 78.2%, respectively. The p16-positive and HPV-positive groups demonstrated significantly increased cause-specific survival in comparison with their negative counterparts.

Primary non-Hodgkin's lymphoma of the thyroid.

Eighty seven cases of primary non-Hodgkin's lymphoma of the thyroid presenting to the Beatson Oncology Centre were reviewed. Stage IE and Stage IIE disease accounted for 79 of 87 cases. In a univariate analysis the presence of dysphagia, dyspnoea, positive nodes, stage or male sex all had a statistically significant detrimental influence on survival. Stage and dysphagia were the most influential individually and a multivariate analysis indicated that the prognostic information in all these features was essentially captured by just these two. A prognostic scoring index based upon stage of disease and the presence of dysphagia has been developed. Overall 5 year survival was 43%. Five year survival for Stage IE patients without symptoms of compression was 74%. Patients who underwent surgical resection of tumour followed by local irradiation appeared to survive longer than patients managed by irradiation without surgery, although after adjustment for prognostic features this advantage was not statistically significant.

Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy.

Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dysphagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy.

An audit of travel and waiting times for outpatient radiotherapy.

The object of this study was to assess the non-medical factors which detract from the quality of outpatient receiving service to a population of 2.7 million in a wide geographical area. We conducted a survey by patient questionnaire of all outpatients receiving radiotherapy in the West of Scotland on a single day in 1990. A total of 216 outpatients attended for radiotherapy with a 92% response rate to the questionnaire being achieved. Median values (and ranges) were: age 58 (4-85) years, number of daily treatments 20 (4-33), distance travelled in one direction 10 (1-60) miles, travelling time 45 (5-130) minutes, waiting time in the unit for treatment 60 (0-200) minutes, and a time away from home of 2 hours 50 minutes (35 minutes-7 hours). Sixteen per cent of patients had a relative who lost time from work by transporting the patient and only 12 of 60 patients who were away from home over a meal time were offered a hospital meal. Sixteen per cent of patients came by ambulance and 73% by motor car. Of 146 travelling by car 27% used a charity service and 20% a volunteer driver ambulance service car. It is concluded that long travelling distances, travelling times and treatment waiting times for many patients require revision of transport provision, a strict appointment system, more treatment machines and hostel accommodation.

Carboplatin, 5-fluorouracil and folinic acid: a 48-hour chemotherapy regimen in advanced and recurrent squamous carcinoma of the head and neck.

Eighty patients with advanced squamous carcinoma of the head and neck were entered into a study using a 2-day, inpatient, intravenous regimen. Folinic acid 200 mg/m2, 5-fluorouracil (5-FU) 500 mg/ m2 bolus followed by 5-FU 500 mg/m2 in a 22-hour infusion were given on days 1 and 2, with carboplatin 300 mg/m2 on day 2. The whole was repeated every 21 days. Forty-three patients had advanced disease with no prior treatment; 37 had recurred following radical treatment. Fifty-eight patients were male and the median age was 60 years. In total, 275 cycles of chemotherapy were given. The major toxicity was haematological, which delayed 65 cycles of chemotherapy and contributed to the death of two patients. Non-haematological toxicity was mild, with less than 8% of patients experiencing any toxicity greater than WHO grade 2. The patients who had had no previous treatment had a 65% response rate (95% confidence interval (95% CI) 48-80). Those who had been previously treated had a 37% response rate (95% CI 21-55). The overall response rate was 52% (95% CI 40-64), of whom 5% were complete responders. The median survival time was 36 weeks (95% CI 29-45), with the majority of patients dying with progressive disease. We conclude that this chemotherapy regimen was well tolerated and produced minimal toxicity, while maintaining an acceptable response rate of 52%.

Management of ovarian cancer: referral to a multidisciplinary team matters.

Differences in survival outcome for patients with ovarian cancer in Scotland led to an investigation of whether these differences were due to variation in presenting prognostic features or to the organisation and delivery of cancer services. A retrospective study of all 533 cases of ovarian cancer registered in Scotland in 1987 was carried out. After adjustment for age, stage, pathology, degree of differentiation and presence of ascites, survival improved when patients (1) were first seen by a gynaecologist (P < 0.05); (2) were operated on by a gynaecologist (P < 0.05); (3) had residual disease of less than 2 cm post-operatively (P < 0.001); (4) were prescribed platinum chemotherapy (P < 0.05); and (5) were referred to a joint clinic (P < 0.001). When gynaecologists operated the likelihood of smaller residual disease increased (P < 0.001). The improved survival from management by a multidisciplinary team at a joint clinic was not solely due to the prescription of platinum chemotherapy. The results of this study support the contents of the 1991 Department of Health report on present acceptable practice in the management of ovarian cancer, circulated to gynaecologists and surgeons in Scotland in 1992. The new finding that in a common cancer management by a multidisciplinary team at a joint clinic directly affects survival requires urgent attention.

Survival of younger cervical carcinoma patients treated by radical radiotherapy in the west of Scotland 1964-1984.

Between 1964 and 1984, 2011 patients in the West of Scotland were treated by radical radiotherapy for carcinoma of cervix. In keeping with the rise in incidence amongst younger patients nationally, the number of women aged less than 35 years seen during the 20-year period has doubled. Younger women (aged less than 35 or less than 45) have a better prognosis mainly because more present with earlier disease. Stage for stage there has been no change in survival of women of all ages treated by identical radiotherapy during this period. The rise in mortality of younger patients from carcinoma of cervix may be due to the increased incidence of the condition rather than a more virulent form of the disease.

Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients.

OBJECTIVE: To determine whether specialist gynaecological surgeons improved survival in women with ovarian cancer when compared with general gynaecologists. DESIGN: Retrospective case note review. POPULATION: All women diagnosed with ovarian cancer in Scotland in 1987, 1992, 1993 and 1994. METHODS: Data on prognostic factors and surgical and post-operative management was extracted from case notes. Surgeons were classified as specialist gynaecologists, general gynaecologists or general surgeons by an independent committee with no knowledge of an individual's outcome. Cox's proportional hazards model was used to determine the relative risk of a patient dying, if managed by specialist and general gynaecologists, after adjustment for age, histology, tumour differentiation, presence of ascites and socio-economic status. Analysis was performed separately for each FIGO stage. MAIN OUTCOME MEASURES: Relative hazard ratios for survival up to three years. RESULTS: Survival benefit for specialists varied according to the stage of the disease. The greatest benefit was observed among women with Stage III disease (44% of women presented at this stage) where there was a 25% (relative hazard ratio = 0.75, P = 0.005) reduction in the rate of dying for women operated on by specialist gynaecologists, compared with women operated on by general gynaecologists. Differential use of platinum chemotherapy did not explain this survival advantage. Specialist gynaecologists more often debulked tumour to < 2 cm than general gynaecologists in Stage III cases (36.3% vs 28.7%, P = 0.07). In women with Stage III carcinoma with > 2 cm remaining, survival was significantly improved for women treated by specialist gynaecologists (relative hazard ratio = 0.71, P = 0.007). No significant differences were observed for patients with Stages I, II and IV disease, although there were fewer deaths in women with early stage disease. CONCLUSIONS: Specialist gynaecologists improve survival for some women with ovarian cancer.