A phase II study of oral eniluracil/fluorouracil in patients with anthracycline-refractory or anthracycline- and taxane-refractory advanced breast cancer.

BACKGROUND: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase, the initial and rate limiting enzyme in the catabolism of fluorouracil. The current study was done to determine the objective tumour response of a 28-day oral regimen of eniluracil-fluorouracil in patients with advanced breast cancer. PATIENTS AND METHODS: This was a multicentre, phase II study in patients with anthracycline-refractory (AR) or anthracycline- and taxane-refractory (ATR) advanced breast cancer. Oral eniluracil (10 mg/m2) and fluorouracil (1 mg/m2) were taken twice daily for 28 days of each 35-day treatment course. RESULTS: In this study, 106 patients received treatment: 62 patients in the AR stratum and 44 patients in the ATR stratum. The objective tumour response rate in the intent-to-treat population was 18% (95% confidence intervals (CI): 11%-27%), including three complete responses. The response rate was similar in both strata: 19% in the AR and 16% in the ATR stratum. The overall median duration of response was 23.6 weeks. The treatment was well tolerated with a low incidence of grade 3 or 4 toxicities that were considered attributable to study medication. CONCLUSION: Treatment with oral eniluracil-fluorouracil was well tolerated by patients with advanced breast cancer. The efficacy data were comparable with those of other published studies in this group of refractory patients.

FILM (5-fluorouracil, ifosfamide, leucovorin and mitomycin C), an alternative chemotherapy regimen suitable for the treatment of advanced breast cancer in the 'out-patient' setting.

FILM, a combination of 5-fluorouracil (5-FU) 750 mg/m(2), ifosfamide 1 g/m(2), leucovorin 200 mg/m(2) and mitomycin C 6 mg/m(2) (alternate cycles), was administered to 24 chemo-naive patients with inoperable disease, locally advanced or metastatic. Up to 6 x 3-weekly cycles of FILM were administered on an out-patient basis. Responses included 8 patients in complete remission (CR) and 12 showing a partial response (PR) (83%). Following analysis of these results, the FILM regimen was introduced as a standard out-patient protocol at the North Middlesex Hospital, United Kingdom. A further 66 patients have been treated in this setting. Retrospective analysis of these data confirm the trial results and allow conclusions regarding tolerability, toxicity, duration of response and survival to be drawn from a total cohort of 90 patients. A total of 524 cycles have been administered. Nineteen cycles (4%) were delayed owing to slow recovery of white blood cells (WBC), but no dose reductions were necessary. Five blood transfusions were required for anaemia. The most frequent non-haematological toxicities included nausea, vomiting and fatigue. Of 80 patients treated for inoperable or locally advanced disease, 56 (70%) remain in remission, and 69 (86%) remain alive after 5 years.

Ondansetron suppository: a randomised, double-blind, double-dummy, parallel-group comparison with oral ondansetron for the prevention of cyclophosphamide-induced emesis and nausea. The Ondansetron Suppository emesis study group.

This multinational, multicentre, randomised, parallel-group study compared the safety, tolerability and efficacy of ondansetron 8 mg orally twice a day with ondansetron suppository 16 mg once daily in patients receiving cyclophosphamide-containing chemotherapy. A total of 406 patients were randomised to receive ondansetron 8 mg p.o. (198 patients) or ondansetron suppository (208 patients) medication in a double-blind, double-dummy trial. The primary efficacy analysis revealed that ondansetron provided good anti-emetic control with 81% of patients in the 8 mg p.o. b.d. group and 73% of patients in the 16 mg ondansetron suppository o.d. group experiencing complete or major control of emesis (< or = 2 emetic episodes) on the worst day of days 1-3. The 90% confidence interval for the difference between the two treatments for complete or major control (1.4, 15.0%) showed that the treatments could be regarded as equivalent. A difference in favour of oral ondansetron treatment was noted for the complete control (0 emetic episodes) rates over days 1-3, but no differences were found on day 1. There were no significant differences in the distribution of nausea grades between the treatment groups on the worst day of days 1-3 or on day 1. The incidence of adverse events was similar for the two treatment groups, the most frequently reported events were headache and constipation. There were no significant laboratory findings in either treatment group. In conclusion this study showed that the ondansetron treatments could be regarded as equivalent for the primary efficacy endpoint and that ondansetron suppository was well tolerated and effective in the prevention of cyclophosphamide-induced emesis.

Single-agent paclitaxel as first-line treatment of metastatic breast cancer: the British experience.

The efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was studied as first-line treatment for 30 consecutive patients with metastatic breast cancer. All patients had received adjuvant/neoadjuvant chemotherapy, 22 had prior hormonal therapy, and 26 had received previous adjuvant radiotherapy. Paclitaxel 225 mg/m2 was given as a 3-hour infusion without colony-stimulating factor support at 3-week intervals without excessive dose reduction or delays. The most common nonhematologic toxicities were alopecia (grade 3 in 29 patients) and peripheral neuritis (grade 2 or 3 in 14 patients). The objective response rate was 60% and responses were seen in all disease sites. The median duration of overall response was 30 weeks (range, 15 to 75+ weeks) and the estimated median survival time for all patients was 56 weeks (range, 1 to 82+ weeks). The response rate and survival times seen with single-agent paclitaxel are encouraging. Future studies must explore paclitaxel in combination with other regimens, with the hope that results will improve further.

A phase II study of single agent paclitaxel in patients at first relapse following initial chemotherapy for breast cancer.

This study was initiated to evaluate the safety and efficacy of 3-weekly paclitaxel given at 225 mg/m2 over 3 hours without colony stimulating factor support in patients at their first relapse following adjuvant therapy for breast cancer. Thirty patients were entered into the study; all were assessable for response and toxicity. All patients had received adjuvant/neo-adjuvant chemotherapy; 22 patients had had prior hormonal therapy and 26 previous adjuvant radiotherapy. The group was characterized by a short time to first relapse (median 7.5 months (range 2-43)) and widespread disease, with 22 patients having multiple disease sites including: nodes (43%), skin and soft tissue (43%), liver (40%), lung (37%) and bone (50%). A total of 219 cycles of paclitaxel were given, with a median of eight per patient. The major non-haematological toxicities were: grade 3 alopecia (82% cycles), grade 2/3 arthralgia/myalgia (26%), grade 2/3 fatigue (16%) and grade 2/3 peripheral nervous system toxicity (12%). Haematological toxicity was mainly neutropenia of short duration, with grade 4 counts documented in 16% of cycles. Thrombocytopenia was minimal and there were no significant hypersensitivity reactions. The objective response rate was 60% (95% CI 42.5-77.5) with one complete response and 17 partial responses. The median duration of overall response was 30 weeks (range 15-75+ (95% CI 25-33)) with a median survival time for all patients of 42 weeks (range 1-124+). This study demonstrates that paclitaxel 225 mg/m2 is well tolerated as a 3-hour infusion and can be given safely in an outpatient setting without routine use of granulocyte colony stimulating factor. The response rate is encouraging and shows that this regimen is effective in this poor prognosis patient population.

Single-agent paclitaxel at first relapse following adjuvant chemotherapy for breast cancer.

The efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was studied in 27 patients who had relapsed following adjuvant/neoadjuvant chemotherapy for breast cancer. Paclitaxel 225 mg/m2 given as a 3-hour infusion is an effective regimen in this poor-prognosis population. It is well tolerated and can be given in an outpatient setting without routine use of granulocyte colony-stimulating factor. It also can be given in repeated cycles without excessive dose reductions or delays. An objective response rate of 54% was obtained. Responses were seen at all disease sites. Future studies must explore a paclitaxel-containing combination regimen to improve response rates further.

Oral cavity metastasis from carcinoma of the cervix.

A case report of a patient with carcinoma of the cervix with metastasis to the oral cavity clinically mimicking a primary oral cavity neoplasm is described. The patient presented one year after completing radiotherapy followed by radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix. Excellent palliation was produced with radiotherapy. We are not aware of any reported case of oral cavity metastasis from carcinoma of the cervix.

Brain metastasis from basaloid carcinoma of the anal canal 8 years after abdominoperineal resection.

Basaloid carcinoma of the anal canal is a rare tumour originating from a persistent remnant of the cloacal membrane of the embryo. Wide abdominoperineal resection is the treatment of choice with a 5-year survival rate of 50%. A case of brain metastasis 8 years after abdominoperineal resection is reported. Postoperative radiotherapy may eradicate subclinical disease and prolong survival.

Prechemotherapy serum CA125 level as a predictor of survival outcome in epithelial carcinoma of the ovary.

A total of 55 patients with epithelial ovarian carcinoma treated with platinum-based chemotherapy were followed for a minimum period of 2 years. Of these 22 patients had a prechemotherapy serum CA125 level of less than 50 ku/l and 33 patients had a serum CA125 level of greater than or equal to 50 ku/l. The 5-year actuarial survival of the two groups were 75% and 10% respectively. Prechemotherapy CA125 level taken 4 weeks after debulking surgery may predict the eventual survival outcome in epithelial ovarian cancer patients who undergo chemotherapy treatment.

Tracheal infiltration causing stridor: a rare presentation of stage I Hodgkin's disease.

Tracheal neoplasms are easily missed until a late stage, but an accurate histological diagnosis can lead to a very worthwhile result. A case of Hodgkin's disease presenting with stridor due to tracheal infiltration, diagnosed following an endometrial biopsy and treated successfully with external beam radiotherapy, is here reported upon.

Advanced ovarian cancer: long-term results following chemotherapy and second-look laparotomy.

Thirty patients who showed a complete clinical response to cis-platinum-containing combination chemotherapy underwent second-look laparotomy. Seventeen patients (56.7%) achieved a pathologically confirmed complete remission as documented by a negative second-look laparotomy. After a minimum follow-up of 60 months, 6 of 17 patients developed recurrent disease and subsequently died. Due to the occurrence of late relapse in these negative second-look patients routine second-look laparotomy to confirm pathological response cannot be justified. Ten of thirty patients underwent secondary cytoreductive surgery at second-look operation. All ten patients had suboptimal initial debulking surgery. Five of these ten patients (50%) survived 4 years. Secondary cytoreductive surgery may improve survival in patients who undergo suboptimal initial debulking surgery.

Influence of microscopic residual disease on survival for stage IB and IIA carcinoma of the cervix following intracavitary irradiation.

From 1977 to 1982, 102 patients with Stage IB and IIA carcinoma of the cervix underwent preoperative intracavitary caesium irradiation followed by radical hysterectomy and pelvic lymphadenectomy at the Wessex Radiotherapy Centre. The actuarial 5-year survival rate for Stage IB is 80% and for Stage IIA is 62%. Patients who had microscopic residual disease in the hysterectomy specimen and negative nodes showed an actuarial 10-year survival rate of 62% as opposed to 82% in patients with no residual disease and negative nodes (P less than 0.05).

Long-term survival after chemotherapy with cisplatinum, adriamycin and cyclophosphamide for carcinoma of the ovary.

Forty six patients with FIGO Stage II, III, and IV ovarian cancer received treatment with cisplatinum, adriamycin and cyclophosphamide. After a minimum follow-up time of 60 months 13 patients remain free of recurrence. The overall 5-year survival is 39% and the median survival is 39 months. The 5-year survival for Stages II, III, and IV is 64%, 40% and 0% respectively. The 5-year actuarial survival for those who had less than 2 cm residual disease (including those with complete debulking) is 72%, while for those who had greater than 2 cm residual disease (including those who had biopsy only) is 15%. None of the patients have developed any second neoplasm.

Cosmetic results of early breast carcinoma treated with wide local excision, external beam radiotherapy and iridium-192 boost.

Cosmetic results of 80 patients with axillary lymph node negative or unknown T1 and T2 carcinoma of the breast who were treated with wide local excision, external beam radiotherapy and iridium-192 boost, were evaluated by the patient and the radiotherapist at 18-36 months. Their overall cosmetic results were assessed as good, very good or excellent by 80% of the patients. The radiotherapist's assessment was similar but in general the patients score was more favourable. After a follow-up of 24-72 months recurrence was found in only one patient at 40 months. This approach offers good cosmesis with low local recurrence rates in early breast carcinoma patients with negative axillary lymph nodes.

Primary non-Hodgkins lymphoma of the bladder. Case report and review of the literature.

Primary lymphoma of the bladder is a rare disease. It is usually localised for long periods. With modern radiotherapy treatment prognosis is excellent. A case report is described and the clinical, pathological and therapeutic aspects of the disease are reviewed.

Tongue metastasis from carcinoma of the rectum.

A case report of a patient with carcinoma of the rectum with metastasis to the tongue clinically mimicking a primary tongue neoplasm is described. The patient presented with an ulcer in the tongue three years after undergoing an anterior resection for a Dukes C carcinoma of the rectum. Other asymptomatic metastatic lesions were discovered only after the histology report suggested that the tongue ulcer biopsy was metastatic in origin. Metastatic tumour to the tongue is extremely rare and often occurs at a late stage, when there is disseminated disease. We are not aware of any reported case of tongue metastasis from carcinoma of the rectum.

Systemic metastasis from primary intracranial germinoma: a case report and literature review.

A case of systemic haematogenous metastasis occurring post-operatively from a primary suprasellar intracranial germinoma is reported. While local invasion and direct spread associated with surgical incision and shunt procedures are well known, haematogenous metastasis of these tumours is extremely rare. Problems associated with establishing this diagnosis are discussed.

Self-reported use of alcohol, cigarettes, tranquillisers and sedatives in patients admitted to a general hospital.

The relation between alcohol and hospital admissions and the patterns of use of cigarettes, tranquillisers and sedatives was studied in a sample of 339 consecutive admissions to Northland Base Hospital. Also examined was the usefulness of serum gamma glutamyl transferase (GGT) and blood ethanol as screening tests for high alcohol use in general hospital patients. A short multiple choice questionnaire was used, completed answers being obtained from 91.7 percent of the sample; GGT estimations were done on 64 percent and blood ethanol on 38 percent of the sample. Alcohol was considered to be a factor in the admission of at least 6.4 percent of the total sample. Blood ethanol estimations were not found useful as a screening test but GGT had a specificity of at least 27 percent for diagnosing high alcohol use in the general hospital situation. The regular use of tranquillisers and sedatives in elderly non-Maori patients was high but appears rare in Maoris of all ages.