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ABSTRACT: In the treatment of operable breast cancer by breast conservation, the extent of axillary dissection, the need for radiotherapy to the axilla and the morbidity associated with these procedures have not been assessed adequately.
Patients with operable breast cancer were randomized to have level III axillary node clearance (232 patients) or axillary node sample (234 patients). Radiotherapy to the axilla was given selectively. Radiotherapy was not given to those who had an axillary clearance. In the early part of the study all patients who had node sample were treated by radiotherapy (54 patients); subsequently this was modified to include only those who were node positive. The morbidity to the shoulder and arm was assessed before and after operation by measuring upper limb volume and circumference, and combined glenohumeral and scapular movement and muscle power.
Comparing the two surgical policies, no difference was found in local (axillary clearance 14 versus sample 15), axillary (eight versus seven) or distant (29 versus 29) recurrence. There was no statistically significant difference in 5-year survival rate (clearance 82.1 versus sample 88.6 per cent). Morbidity was least in those who had a node sample and no radiotherapy to the axilla. Radiotherapy to the axilla in patients who had a node sample resulted in a significant reduction in range of movement of the shoulder, e.g. mean(s.e.) 2.2(0.6) cm reduction in lateral rotation at 3 years. Surgical axillary clearance was associated with significant lymphoedema of the upper limb, e.g. 4.1(0.7) per cent increase in arm volume at 3 years.
A selective policy for the management of the axilla is associated with no increase in axillary recurrence or mortality rate compared with routine axillary node clearance. Patients who are node negative after axillary sample can avoid radiotherapy or axillary clearance.
British Journal of Surgery 03/2000; 87(2):163-9. · 4.61 Impact Factor
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ABSTRACT: The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial.
To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases.
In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain.
Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters.
It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.
Radiotherapy and Oncology 12/1997; 45(2):109-16. · 5.58 Impact Factor
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ABSTRACT: In a trial conducted in southeast Scotland between April 1974 and December 1979, 332 women with invasive breast cancer of Stage I and II with histological evidence of node involvement, or who had operable or inoperable Stage III disease, were randomized, after primary local therapy (mastectomy, node biopsy and radiotherapy for all except the inoperable disease patients who underwent radiotherapy alone) to receive 12 4-weekly intravenous injections of 5-fluorouracil (5-FU), 700 mg/m2 or no systemic therapy. After a median follow-up of 15 years from randomization, no difference is shown between the two groups in terms of distant relapse (hazard ratio (HR) = 1.02; 95% CI 0.78-1.32), event free survival (HR = 1.23; 95% CI 0.97-1.56), or total survival (HR = 1.19; 95% CI 0.93-1.52). Locoregional relapse is significantly reduced by 5-FU administration (HR = 1.88; 95% CI 1.20-2.96). The results are similar for the trial as a whole or when mastectomy patients are considered alone. Toxicity was minimal with marrow suppression in only 19 of 147 patients receiving more than one injection; only five patients discontinued therapy due to nausea and vomiting. However, retrosternal pain occurred in 16 patients, nine of whom had their treatment curtailed as a result. Seventy-seven per cent of patients have died, the majority from breast cancer. Only 1.2% of deaths are considered attributable to cardiac causes of 5-FU is not associated with excess cardiac deaths in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Oncology 02/1995; 7(1):7-11. · 2.07 Impact Factor
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BMJ 01/1995; 309(6967):1501-4. · 14.09 Impact Factor
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BMJ 12/1994; 309(6966):1431-3. · 14.09 Impact Factor
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ABSTRACT: J M Dixon acknowledges the support of the Cancer Research Campaign. Photographs of the patient treated by intra-arterial chemotherapy were provided by Mr J R C Sainsbury, consultant surgeon at Huddersfield Royal Infirmary. Other photographs were prepared by Mr D Dirom, Medical Illustration Unit, University of Edinburgh.A Rodger is director of William Buckland Radiotherapy Centre at Alfred Hospital and professor of radiation oncology at Monash University, Melbourne, Australia; R C F Leonard is consultant medical oncologist at Department of Clinical Oncology, Western General Hospital, Edinburgh; and J M Dixon is senior lecturer in surgery at Edinburgh Royal Infirmary and honorary consultant surgeon at Western General Hospital, Edinburgh. The ABC of Breast Diseases has been edited by J M Dixon.Locally advanced disease of the breast is characterised clinically by features suggesting infiltration of the skin or chest wall by tumour or matted involved axillary nodes. Large operable breast cancers and tumours fixed to muscle should not be considered as locally advanced. Depending on referral patterns and clinical definitions, between one in 12 and one in four patients with breast cancer present with locally advanced disease. Reflecting the differences in definition and the variable natural history of breast cancer, reported five year survival varies between 1% and 30%. Median survival is about 2-2.5 years, which is similar to that described for breast cancer in the late 19th and early 20th centuries.
Clinical features of locally advanced breast cancer
Skin
UlcerationDermal infiltrationErythema over tumourSatellite nodulesPeau d'orange
Chest wall Tumour fixation to
RibsSerratus anteriorIntercostal muscles
Axillary nodes
Nodes fixed to one another or to other structures
Locally advanced breast cancer may arise because of its position in the breast (for example, peripheral), neglect (some patients do not present to hospital for month or years after they notice a mass), or biological aggressiveness (this includes all inflammatory cancers and most with peau d'orange). Inflammatory carcinomas are uncommon and are characterised by brawny, oedematous, indurated, and erythematous skin changes and have the worst prognosis of all locally advanced breast cancers.View larger version:In a new windowDownload as PowerPoint SlideFIG
Inflammatory breast carcinoma.
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Peau d'orange associated with breast carcinoma.
Treatment
Current treatments have had some impact on control of local disease but have had little overall effect on metastatic progression, although survival is better with hormone sensitive disease. Local and regional relapse is a major problem and affects more than half of patients.
Role of systemic and local treatment
The mainstay of local treatment has been radiotherapy. This is because surgery, generally mastectomy, results in high rates of local recurrence. In contrast, radiotherapy alone can produce high rates of local remission in both the breast and axilla, but with radiotherapy alone only 30% of patients remain free of locoregional disease at death. A combination of appropriate systemic treatment and radiotherapy can increase the initial rate of local response to over 80%.
Factors affecting choice of systemic treatment for locally advanced breast cancer
Hormonal treatment
Slow growing or indolent diseaseOestrogen receptor positive cancerElderly or unfit patients
Chemotherapy
Inflammatory cancerOestrogen receptor negative cancerRapidly progressive cancer
Choice of systemic treatment
Systemic treatment should be administered as part of a planned programme of combined systemic and local treatment. For frail patients treatment may initially be by tamoxifen, with radiotherapy held in reserve for relapse.
Although standard chemotherapy regimens have increased rates of local control, they have had little impact on survival. Studies are currently under way to determine whether intensifying drug dosage (increasing the amount of drug given in a fixed period either by giving smaller doses more frequently or by combining higher doses with factors to encourage regeneration of bone marrow) does produce survival benefits. Current data suggest that infusional treatment with fluorouracil combined with the anthracyclines doxorubicin or epirubicin in regimens with cyclophosphamide or cisplatin produces higher response rates than intermittent regimens used for adjuvant chemotherapy.
Choice of systemic treatment for locally advanced breast cancer
Hormonal treatment
Premenopausal women—ovarian ablation (surgery, radiation, or gonadotrophin releasing hormone antagonists)Postmenopausal women—tamoxifen
Chemotherapy
Intravenous—infusion of fluorouracil combined with an anthracycline*RF**Intra-arterialFor example, doxorubicin, cyclophosphamide, and fluorouracil; or epirubicin, cisplatin, and fluorouracil.
Radiotherapy
Radiotherapy is generally well tolerated, even by elderly and frail patients. It can be given concurrently with systemic hormonal treatment, or it can be given after a course of primary chemotherapy to patients whose breast cancer still shows signs of local advancement. The breast skin requires full dose, and this will result in temporary erythema and possible desquamation. If possible the palpable tumour masses should receive treatment boosts.
Radiotherapy for locally advanced breast cancer
Treatment areas
Breast o Axilla and supraclavicular fossa
Treatment
Megavoltage x raysTechnique for enhancing skin dose40-50 Gy in 15-25 fractions over 3-5 weeksBoost to tumour mass if possible by external beam or radioactive implant of 10-20 Gy
Toxicity
LethargyTemporary mild dysphagia<3% risk of pneumonitisSkin erythema and small areas of moist desquamation
Surgery
Mastectomy is generally not indicated in the presence of features of locally advanced disease, but the role of surgery is changing. Aggressive treatment with a combination of cytotoxic drugs or initial hormonal treatment often causes the primary tumour to regress to a lower stage (with disappearance of peau d'orange and erythema and reduction in tumour volume), making surgery feasible some weeks or months after the start of systemic treatment. In such cases surgery may be a wide excision and clearance of axillary nodes or a total mastectomy and node clearance, both being followed by radiotherapy to the remaining breast or to the chest wall.
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Mammogram of locally advanced breast tumour (left); and after chemotherapy, showing substantial reduction in tumour volume (right). (Tumour was operable after treatment.)
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Local advanced breast cancer (left); and complete clinical response after chemotherapy (right).
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Locally advanced breast cancer (left); and reduction in size after six months of tamoxifen treatment (right). The mass in the infraclavicular region is a lipoma.
In some patients residual disease remains in the breast despite systemic treatment and radiotherapy. This disease can be excised by a salvage mastectomy, ideally followed by coverage with a myocutaneous flap (from latissimus dorsi or transverse rectus abdominus). “Toilet” surgery, used in an effort to control fungating cancers or recurrence and progression of disease, is often ineffective and should only be performed for breast cancers that are locally advanced either because of their peripheral position in the breast or because of a delay in presentation. In this group surgery should be combined with radiotherapy and appropriate adjuvant systemic treatment.
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Salvage mastectomy and coverage with myocutaneous flap (from latissimus dorsi) for treatment of residual disease after chemotherapy and radiotherapy.
Intra-arterial chemotherapy
Despite the best efforts with combined treatments, a substantial proportion of patients who present with locally advanced disease develop uncontrolled disease of the chest wall. Although low dose intravenous chemotherapy by infusion (for example, infusional fluorouracil) can relieve symptoms in up to half of these patients, the overall efficacy of systemic chemotherapy is poor. Because of technical difficulties, investigation of intra-arterial chemotherapy has been limited to uncontrolled studies in a few centres. However, the best published series report impressive response rates with low toxicity in patients presenting initially with locally advanced breast cancer. If intra-arterial treatment does not produce a response after the first course it is probably not worth pursuing. The drugs and doses used are similar to those given intravenously for palliative treatment. One problem with delivery of drugs by the intra-arterial route is that in patients who have received radiotherapy the blood vessels supplying the chest wall may be damaged, resulting in an impaired blood supply that limits drug delivery.
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Locally advanced breast cancer with ulceration (left); and good response and re-epithelialisation after three courses of intra-arterial chemotherapy (right).
Local recurrence after mastectomy
View this table:View PopupView InlineTreatment of local recurrence in chest wall
This usually occurs in the skin flaps adjacent to the scar and is presumed to arise from viable cells shed during surgery. It can usually be diagnosed by fine needle aspiration cytology. Local disease can be isolated, but in up to half of patients it heralds systemic relapse. For this reason a search for distant metastases should be undertaken in all patients.
Local recurrence after mastectomy can be classified as single spot relapse, multiple spot relapse, or field change. Treatment and prognosis differ for these three categories.
Treatment
If the recurrence is focal and occurs many years after the original surgery excision alone can provide long term control. If the recurrence is not single but still localised then the options are radiotherapy or a more radical excision. In a more widespread recurrence standard treatments are often disappointing, although intra-arterial chemotherapy and infusional fluorouracil are sometimes effective. Failure to halt the progress of local disease can lead to cancer en cuirasse—where the chest wall is encircled by tumour—a most unpleasant situation for the patient.
Recurrence in the chest wall can be quite indolent, grow slowly, and occur in the absence of metastases elsewhere. The control of ulceration and focal malodorous infected tissue is a considerable problem for carers, and patients with such disease have a miserable existence. Excision of dead tissue and the use of topical and oral antibiotics with antianaerobic activity combined with charcoal dressings help to control the malodour. The best form of treatment is prevention by ensuring that initial local treatment is optimal.
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Longstanding, isolated, large, unsightly, and malodorous local recurrence after mastectomy and radiotherapy.
BMJ. 11/1994; 309(6966):1431 - 1433.
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BMJ 04/1994; 308(6930):715. · 14.09 Impact Factor
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ABSTRACT: Eighty-five patients treated with loco-regional radiotherapy to the breast/chest wall and cervico-axillary nodes, and 16 patients treated with local radiotherapy to the breast/chest wall alone for breast cancer were enrolled in a prospective study to measure the effects of treatment on pulmonary function during the acute phase (10 weeks after completing irradiation) and during the late phase (12 months after completing irradiation). Baseline pulmonary function values were obtained from all patients immediately prior to commencing radiotherapy. Twenty-two patients (25.8%) treated with loco-regional radiotherapy developed transient chest symptoms compared with two patients (12.5%) treated with local radiotherapy (P = 0.11). Patients undergoing loco-regional radiotherapy showed a reduction of mean vital capacity of 0.13 litres (4.2%) (P < 0.0001) during the acute phase and at 1 year a further decrease occurred (P = 0.02) so that mean vital capacity was reduced by 0.18 litres (5.8%) (P < 0.0001) compared to pretreatment values. Mean transfer factor for carbon monoxide (TLCO) was reduced by 0.85 mmol.kPa-1.min-1 [11.9%] (P < 0.0001) during the acute phase and remained unchanged at 1 year. Patients undergoing local radiotherapy to the breast/chest wall alone did not show any significant loss of vital capacity but mean TLCO was reduced during the acute phase by 0.65 mmol.kPa-1.min-1 (8.3%) (P < 0.002) which remained unchanged at 1 year. No significant association was found between impairment of ventilation or gas transfer and respiratory history, smoking history, concurrent respiratory symptoms, age, side treated or physiological pulmonary function in either the acute or late phase. This study has quantified some of the physiological sequelae following local and loco-regional radiotherapy for breast cancer. There is no evidence to suggest that any of the above factors are relevant to deciding which patients should, or should not, be offered local or loco-regional radiotherapy for breast cancer.
Radiotherapy and Oncology 01/1994; 30(1):33-42. · 5.58 Impact Factor
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ABSTRACT: Between January 1954 and March 1964, 3926 patients with primary breast cancer were referred to The Department of Clinical Oncology, Edinburgh. One hundred and eighty patients developed 195 malignancies subsequent to the treatment of their initial breast cancer. Overall, the total number of second tumours was not significantly in excess of the expected incidence in the general population. However, statistical analysis revealed a significant increase in the incidence of rectal, skin and bone tumours. The excess of bone tumours was likely due to radiation exposure. There was not an overall excess of tumours within the irradiated or scattered radiation volume.
Radiotherapy and Oncology 03/1993; 26(2):125-31. · 5.58 Impact Factor
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ABSTRACT: The pathological features of 236 clinical stage I and II invasive breast carcinomas treated by conservation were reviewed. On follow-up (minimum 2 years) 13 patients (6%) have developed breast relapse, 10 (4%) regional lymph node relapse and 26 (11%) distant metastases. Nineteen patients have died from breast carcinoma. On univariate analyses lymph node metastases, increasing amounts of non-invasive carcinoma and multiple foci of invasion were significant risk factors for breast relapse. A Cox's multivariate analysis showed the first two of these to be independently significant. The results are in agreement with other published series and confirm that assessment of non-invasive carcinoma is important. The study compares simple quantitation with the original method reported to define cases with an "extensive intraduct component".
Radiotherapy and Oncology 12/1992; 25(3):176-80. · 5.58 Impact Factor
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ABSTRACT: Fifty-four consecutive patients underwent 61 orthopaedic operations for metastatic bone disease affecting the upper and lower limbs. These patients were subsequently managed using a consistent postoperative radiotherapy (RT) policy. There were 27 prophylactic internal fixations and 34 internal fixations of pathological fractures. There was a marked difference in survival between these groups. The median postoperative survival of the prophylactic (P) group was 15 months whereas that of the fracture (F) group was 2 months (P less than 0.0001). Ninety-three per cent of the P group and 59% of the F group were able to be discharged home following treatment. Subsequent local fracture requiring further surgical intervention occurred in 11% of the P group and in none of the F group. Seventy-eight per cent of the P group and 62% of the F group did not suffer any further sequelae at the operation site until the time of death or last follow-up. Patient mobility following surgery and RT for metastatic lesions occurring in the lower limb was significantly improved in both the P group (P less than 0.05) and in the F group (P less than 0.0001) such that 91% and 58%, respectively, of these patients were subsequently able to walk.
Clinical Oncology 08/1992; 4(4):244-8. · 2.07 Impact Factor
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ABSTRACT: In Edinburgh in 1982, radiotherapy for patients with T4 breast cancer was modified by an increase in tumour absorbed dose from 42.5-45.0 Gy to 60-75 Gy by using tumour boosts and changing from alternate day to daily fractions. To assess whether this improved local control or survival, the records of all females with T4-N0-3M0 breast cancer referred between January 1978 and December 1985, who received radiotherapy without initial mastectomy or adjuvant chemotherapy, were reviewed. There were 193 patients in the study. Minimum follow-up was 36 months. Actuarial survival at 5 years was 27.1% and median survival 29 months. Local control was achieved by 25.9%. On multivariate analysis, the probability of survival fell with increasing tumour size, advanced clinical node status and the presence of inflammatory change. Radiotherapy technique also affected prognosis. Four-field techniques were associated with a better chance of survival than the breast and axillary jig or other treatment methods. The probability of local control increased with reduced tumour size and showed the same relationship to radiotherapy technique as did survival. Dose was not a significant variable for either survival or local control. No improvement in survival or local control was apparent in comparison with a previous study. It is concluded that radiotherapy alone at a dose of 60 Gy is insufficient to produce durable local control for the majority of women with T4 breast cancer.
Clinical Oncology 08/1992; 4(4):217-21. · 2.07 Impact Factor
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ABSTRACT: Twenty-four evaluable patients with stage T4 breast cancer were entered into a phase II study and received chemotherapy comprising cyclophosphamide 1,000 mg m-2 i.v., doxorubicin 50 mg m-2 i.v., vincristine 1.4 mg m-2 i.v. and prednisolone 40 mg orally for 5 days, given 3 weekly for four cycles prior to undergoing loco-regional radiotherapy. All patients completed treatment as planned with no major acute toxicity from either chemotherapy or radiotherapy. Subsequently 52 patients with stage T4 breast cancer were randomised in a phase III trial to receive either radiotherapy alone (RT) or this chemotherapy and radiotherapy (CHOP + RT). A significantly higher complete response rate was achieved in the CHOP + RT treatment arm (P = 0.03). However a larger proportion of the RT arm achieved loco-regional control after salvage treatment for relapse such that 50% of the RT arm and 57% of the CHOP + RT arm had no evidence of loco-regional disease at the time of last follow-up or death. There was no statistical difference in time to distant relapse or overall survival. Analysis of the pilot study showed results comparable to the trial CHOP + RT arm. This trial suggests that this cytotoxic therapy used in conjunction with radiotherapy has only marginal value in improving prognosis in locally advanced breast cancer.
British Journal of Cancer 06/1992; 65(5):761-5. · 5.04 Impact Factor
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ABSTRACT: The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study.
British Journal of Cancer 06/1992; 65(5):766-8. · 5.04 Impact Factor
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British Journal of Surgery 03/1992; 79(2):184. · 4.61 Impact Factor
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ABSTRACT: Physicists, radiotherapists and radiographers have worked together to enhance the quality and accuracy of radiotherapy for tangential irradiation of the chest wall and breast. Each stage of the process has been reassessed and improved. A technique has been developed on the treatment simulator which determines the required beam directions and sizes in a straightforward manner. A computerised tomography facility has also been developed on the simulator and this provides one or more slices for planning through the treatment volume, thus allowing accurate determination of external contour and lung position with the patient in the treatment position. The beam edge entry points and the isocentre position can be seen from radiation opaque markers placed on the skin surface, allowing accurate reproduction of the treatment beam positions as set on the simulator. A photon beam algorithm that corrects for the changes in scatter dose in a 3-dimensional (3-D) inhomogeneous situation has been developed and applied to tangential chest wall irradiation. This has shown large differences (up to 10%) in dose compared to a conventional 2-dimensional algorithm. The changes in dose distribution due to the accurate determination of lung position have also been investigated. A method has been developed of measuring the volume of ipsilateral lung irradiated. Dose-area histograms are used to evaluate the fraction of the lung area irradiated in the central slice, and an estimate of the volume irradiated can be made using a beam's eye radiograph and the simulator CT image.
Radiotherapy and Oncology 03/1992; 23(2):118-26. · 5.58 Impact Factor
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BMJ 12/1991; 303(6813):1335. · 14.09 Impact Factor
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ABSTRACT: Between 1977 and 1983 100 elderly women (median 76.3 years) with breast cancer were treated with tamoxifen as primary therapy. The median follow-up is 59 months. Sixty-eight responded (40 CR and 28 PR) with median response durations of 47 months and 26 months respectively. Twenty-two patients had disease stabilization for a median of 15.5 months and 10 had progressive disease. The median time to best response was 13.5 weeks for patients achieving CR and 14 weeks for those with PR. Oestrogen receptor values were obtained in 37 patients of which two patients had no ER detectable. Sixty-seven per cent of ER-unknown patients responded compared with 74% of ER-rich. Likelihood of response did not appear to depend upon T-stage or age. Survival was better than that of an unmatched historical group treated with surgery/radiotherapy and compares favourably with recent reports. Although 35% have died of breast cancer, 25% died of other causes and 22% remained free of recurrence at the time of reporting or at death. Only 11% underwent subsequent mastectomy/lumpectomy and the most frequent subsequent treatments were radiotherapy to the breast (32%) and further hormonal therapies (40%). Tamoxifen is a practical primary therapy of breast cancer in elderly and frail women obviating the need for surgery in a high proportion of cases.
European Journal of Surgical Oncology 03/1991; 17(1):30-5. · 2.50 Impact Factor
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BMJ 03/1991; 302(6771):272. · 14.09 Impact Factor
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ABSTRACT: The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.
Cancer Chemotherapy and Pharmacology 02/1991; 28(5):402-4. · 2.83 Impact Factor
