Results of a survey of the role of multidisciplinary team coordinators for colorectal cancer in England and Wales.

OBJECTIVE: Over the last 6 years, multidisciplinary teams (MDTs) have been established and play a key role in organizing the delivery of cancer care in the UK. There are no published data on the roles of their co-coordinators. To seek the views of colorectal multidisciplinary team co-ordinators (MDTCs) on what they do and how they do it. METHOD: Questionnaires were sent to the colorectal MDTC, or equivalent, in all 180 NHS hospital trusts in England and Wales where colorectal cancer surgery is performed. RESULTS: There was a 70% response rate. Seventy-one per cent of trusts now have a dedicated MDTC, whereas in 2002, only 40% had one. MDTCs generally keep their information on databases, but these differ, and are not coordinated with data entry into the national colorectal cancer database of the Association of Coloproctology of Great Britain and Ireland. In only 26 trusts does the MDTC communicate decisions to primary care, and the patients seem almost completely excluded from this process. CONCLUSION: The recently formed national MDTC Forum should grasp the opportunity of coordinating all of this well-intentioned but pluralistic activity to the benefit of patients, primary care and hospital teams. An effective MDTC with a robust database will be the key in achieving cancer waiting time targets with useful audit, thereby improving patient care.

A cancer research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen.

Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had greater binding affinity for the oestrogen receptor (ER) and reduced agonist activity compared with tamoxifen in preclinical studies. In a randomized phase II trial in 56 postmenopausal patients with progressive locally advanced/metastatic breast cancer we assessed whether idoxifene showed evidence of activity compared with an increased 40 mg/day dose of tamoxifen in patients who had previously demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47 patients eligible for response (25 idoxifene, 22 tamoxifen), two partial responses and two disease stabilizations (SD) for >6 months were seen with idoxifene (overall clinical benefit rate 16%, 95% CI 4.5-36.1%). The median duration of clinical benefit was 9.8 months. In contrast, no objective responses were seen with the increased 40 mg/day dose of tamoxifen, although two patients had SD for 7 and 14 months (clinical benefit rate 9%, 95% CI 1.1-29.2%). Idoxifene was well tolerated and the reported possible drug-related toxicities were similar in frequency to those with tamoxifen (hot flushes 13% vs 15%, mild nausea 20% vs 15%). Endocrine and lipid analysis in both groups showed a similar significant fall in serum follicle-stimulating hormone and luteinizing hormone after 4 weeks, together with a significant rise in sex hormone binding globulin levels and 11% reduction in serum cholesterol levels. In conclusion, while idoxifene was associated with only modest evidence of clinical activity in patients with tamoxifen-resistant breast cancer, its toxicity profile and effects on endocrine/lipid parameters were similar to those of tamoxifen.

A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma.

Bryostatin-1 is a macrocyclic lactone whose main mechanism of action is protein kinase C modulation. We investigated its activity as a weekly 24-h infusion in recurrent ovarian carcinoma. In all, 17 patients were recruited and 11 had chemotherapy-resistant disease as defined by disease progression within 4 months of last cytotoxic therapy. All were evaluable for toxicity and 14 for response. There were no disease responses and the main toxicity was myalgia.

A phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma.

BACKGROUND: The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose of capecitabine when used in combination with epirubicin and cisplatin (ECC) in patients with oesophageal or gastric adenocarcinoma. Response rate, progression-free survival (PFS) and overall survival were also determined, and the effect of previous oesophago-gastric surgery or concurrent oesophago-gastric cancer on the absorption and metabolism of capecitabine was evaluated. PATIENTS AND METHODS: Patients with inoperable oesophago-gastric adenocarcinoma received up to six cycles of epirubicin (50 mg/m(2) i.v., 3-weekly), cisplatin (60 mg/m(2) i.v., 3-weekly) and capecitabine, the latter administered orally in an intermittent schedule (14 days treatment; 7-day rest period) at 3-weekly intervals. Patients were recruited into one of four escalating dose cohorts (500, 825, 1000 and 1250 mg/m(2) bd). Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level, with DLT assessed on the toxicity of the first cycle only. Blood sampling for pharmacokinetic analyses was performed over the first 10 h of day 1 of cycle 1. RESULTS: Thirty-two patients, median age 63 years (range 32-76 years), ECOG performance status < or =2 with locally advanced (10) or metastatic (22) disease were recruited and were evaluable for toxicity. Two of five patients experienced DLT at 1250 mg/m(2) bd with grade II stomatitis (one patient) and grade III diarrhoea with febrile neutropenia (one patient). Cumulative toxicity for all cycles (n = 140) (worst grade per patient) includes grade IV oesophagitis (one patient), grade III diarrhoea (five), grade IV neutropenia with infection (seven), grade II stomatitis (four) and grade IV thrombocytopenia (one). Of 29 patients with evaluable disease, there was one complete response and six partial responses [24% response rate [95% confidence interval (CI) 10% to 44%]], a median PFS of 22 weeks (95% CI 17-27 weeks) and median overall survival of 34 weeks (95% CI 19-49 weeks). Capecitabine was rapidly absorbed after oral administration, with a t(max) of 1-2 h for capecitabine, DFCR (5'-deoxy-5-fluorocytidine) and DFUR (5'-deoxy-5-fluorouridine). The C(max) and AUC(0-)( infinity ) for capecitabine, DFCR and DFUR were similar to those observed in previous monotherapy studies of capecitabine taken after food. CONCLUSION: A dose of 1000 mg/m(2) bd of capecitabine is recommended for use on an intermittent schedule in combination with these doses and schedule of epirubicin and cisplatin. This regimen is tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III comparison with ECF is justified.

A phase II trial of bryostatin 1 in patients with non-Hodgkin's lymphoma.

Bryostatin 1 is a naturally occurring macrocyclic lactone with promising antitumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Hodgkin's lymphoma of indolent type (NHL), previously treated with chemotherapy, received a median of 6 (range 1-9) intravenous infusions of 25 microg/m(2) bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 months. The principal toxicities were myalgia and phlebitis. Treatment was discontinued early because of toxicity alone (phlebitis) in 2 patients, toxicity in addition to progressive disease in 3 patients (myalgia and phlebitis n = 2; thrombocytopenia n = 1) and progressive disease in 5 patients. The results fail to demonstrate efficacy of this regimen of bryostatin 1 in the treatment of NHL. In light of preclinical data that demonstrate synergy between bryostatin 1 and several cytotoxic agents and cytokines, clinical studies to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studies to avoid phlebitis.

A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric adenocarcinoma.

BACKGROUND: The aim of this study was to evaluate the efficacy of the combination of epirubicin, cisplatin and ralitrexed (Tomudex). ECT, in patients with advanced oesophageal or gastric adenocarcinoma. Efficacy was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Twenty-one patients with histologically and/or cytologically proven unresectable (7) or metastatic (14) gastro-oesophageal adenocarcinoma, who had bi-dimensionally measurable disease, with ECOG performance status < or = 2. with adequate haematological, hepatic and renal function received first-line chemotherapy with epirubicin (50 mg/m2). cisplatin (60 mg/m2) and Tomudex (2.5 mg/m2), ECT, at three-weekly intervals. Treatment consisted of three cycles of chemotherapy, with a further three cycles if there was disease response or stabilisation. RESULTS: ECT is an active regimen in the treatment of advanced gastro-oesophageal adenocarcinoma with an overall intention-to-treat response rate of 29% (95% confidence intervals (CI): 11%-52%). In addition, 4 (19%) patients had stable disease. Median time to progression was 19 weeks (95% CI: 7-31 weeks). Median overall survival was 18 weeks (95% CI: 11-24 weeks). Seventeen patients failed to complete the six cycles of treatment due to disease progression (5). toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severe allergy to epirubicin (1), patient decision (1) and five patients after the study was discontinued early due to toxicity. There were three toxic deaths: two due to sepsis complicating neutropaenia and one due to cardiorespiratory failure following drug induced enteritis. Nine patients experienced grade 3 or 4 neutropaenia, two patients experienced grade 3 or 4 nausea and vomiting and one patient had grade 4 diarrhoea. CONCLUSIONS: The combination of epirubicin, cisplatin and tomudex is active against advanced gastro-oesophageal adenocarcinoma but the toxicity suggests that further evaluation in a randomised comparison to ECF is not appropriate.

Non-infusional 5-fluorouracil, doxorubicin and cisplatin in the treatment of locally advanced or metastatic gastro-oesophageal adenocarcinoma.

To reduce the Hickman line-associated morbidity of continuous infusion 5-fluorouracil combined with epirubicin and cisplatin (ECF) and to investigate the need for infusional regimens, we conducted a retrospective study in patients with advanced gastro-oesophageal adenocarcinoma. Thirty-six patients, with histologically proven irresectable gastro-oesophageal adenocarcinoma were given: 60 mg/m2 cisplatin on day 1, 35 mg/m2 doxorubicin on day 1 and 500 mg/m2 5-fluorouracil on days 1 and 8 (NIACF) every 3-weeks. A median of 3 cycles was administered. The principal toxicity was myelosuppression with grade III/IV neutropenia in 47% of cycles. Neutropenic fever occurred in 5% of the cycles: non-haematological toxicity was mild and there were no treatment-related deaths. Administered dose intensity was 96.1% for doxorubicin, 93.6% for cisplatin and 90.5% for 5-fluorouracil. There were 16 partial responses and 1 complete response (overall response rate 47%, 95% confidence interval CI 31-63%); 8 patients had stable disease. Median progression-free and overall survival rates were 5 months (95% CI 4-6) and 8 months (95% CI 6-10), respectively. NIACF is a well-tolerated regimen in advanced gastro-oesophageal adenocarcinoma that precludes the need for central venous access, with activity similar to that observed with ECF.

Metastatic extragonadal seminoma associated with cardiac transplantation.

A 37-year-old man who had successfully undergone cardiac transplantation for dilated cardiomyopathy presented with a history of severe pain over his left shoulder, rib cage and thoracic spine. Clinical examination revealed the presence of bony tenderness over these sites, but there was no other clinical evidence of malignancy. Further investigations suggested the presence of multiple bony metastases. Bone biopsy revealed extensive bone marrow infiltration by large undifferentiated cells showing pronounced cytoplasmic vacuolation with a striking granulomatous reaction. Immunocytochemistry revealed these anaplastic cells to be cytokeratin and placenta-like alkaline phosphatase positive but S100, CD30 and lymphoid marker negative. Analyses by in situ hybridisation of these cells revealed no evidence of Epstein-Barr virus infection. Overall the pathology suggested a diagnosis of metastatic seminoma. Confirmation of this diagnosis was obtained by the analysis of serum human chorionic gonadotrophin which was elevated at 90 IU/l. In the absence of testicular or retroperitoneal disease, it is very likely that this unusual case of metastatic seminoma was related to the patient's immunosuppressive therapy, which at diagnosis included cyclosporin and prednisolone. The patient was successfully treated with cisplatin based chemotherapy and decreased immunosuppression and remains in complete remission one year after completion of chemotherapy. Seminoma is an uncommon complication of prolonged immunosuppression with very few cases being described in the literature post-organ transplantation. This case shows that the clinical presentation of this treatable tumour in this patient population can be unusual and difficult to diagnose.

Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID)--a phase II study.

PURPOSE: The majority of patients with low-grade non-Hodgkin's lymphoma (LGNHL) are in the older age groups and are thus less able to tolerate aggressive treatment. Chlorambucil, alone and in combination, has been widely accepted as the initial treatment of choice for many years. The availability of an anthracycline which could be given orally in combination with chlorambucil and steroid led us to investigate the efficacy and toxicity of this novel regimen. METHODS: Patients (age less than 70 years) with a histologically confirmed diagnosis of LGNHL (Kiel classification) were eligible for the study if they had no previous chemotherapy. Treatment consisted of chlorambucil 20 mg/ m2 daily for 3 days given on each day in three divided doses, idarubicin 10 mg/m2 for 3 days before breakfast, and dexamethasone 4 mg twice daily for 5 days. All drugs were given orally. Treatment was repeated every 21 days for a maximum of six courses. The regimen was assessed for toxicity and response. RESULTS: A total of 72 patients were registered, and 64 were eligible (median age 52 years). Toxicity was assessed for all cycles given (347). The predominant toxicity was haematological, but in only one course did grade 4 neutropenia (less than 0.5 x 10(9)) occur. Alopecia was not a problem. Full doses of the treatment were administered to 40% of the patients, with no delays or dose reductions. The overall response rate was 83%. Six patients had static disease and two progressed on treatment. Lactate dehydrogenase (LDH) was found to be a good predictor of response to treatment. Of 12 patients documented to have raised LDH, 5 failed to respond to treatment, compared to 1 of 32 patients who had a normal LDH (chi2 10.65, P < 0.002). With a minimum follow-up of 4 years for all patients actuarial 5-year event-free survival was 22% and overall survival was 65%. However, in patients with best and intermediate risk LGNHL (by the SNLG Prognostic Index for Low Grade Disease) overall survival are 88% and 64%, respectively. CONCLUSIONS: This novel regimen was effective and well tolerated.

A dose-finding study of raltitrexed (tomudex) with cisplatin and epirubicin in advanced gastro-oesophageal adenocarcinoma.

The standard treatment for advanced gastro-oesophageal cancer in the UK is epirubicin, cisplatin and continuous infusion 5-fluoruracil by an indwelling central venous catheter (ECF), which has significant morbidity. Raltitrexed (tomudex), a specific inhibitor of thymidylate synthase with a long plasma terminal half-life (50-100 h) has activity in gastro-intestinal tract malignancy. To reduce the Hickman line-associated morbidity of ECF; we have conducted a dose-finding study of tomudex combined with epirubicin and cisplatin. Twenty-four patients (22 males, two female), median age 63 years (range 21-75), ECOG performance status < or =2 with histologically proven, unresectable or metastatic gastric (14 patients), gastro-oesophageal junction (nine patients) or oesophageal (one patient) adenocarcinoma received treatment with 3-weekly cisplatin 60 mg m(-2), epirubicin 50 mg m(-2) and tomudex at doses of 2 mg m(-2), 2.5 mg m(-2) or 3 mg m(-2) in successive cohorts. Six patients were treated per dose level with no intra-patient dose escalation. Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level. After defining the maximum tolerated dose a further six patients were treated at the preceding dose level to assess toxicity at the proposed phase II dose. A total of 102 cycles (50% completed 6 cycles) were administered. The dose-limiting toxicities are neutropenia and diarrhoea occurring in 2/6 patients at the 3 mg m(-2) dose level. Of those patients evaluable for response, there were eight partial and one complete response (overall response rate 38%). The median survival was 9.9 months. ECT is an active regimen in oesophagogastric adenocarcinoma. The recommended dose of tomudex for further study in combination with epirubicin and cisplatin is 2.5 mg m(-2).

Therapeutic implications of the sentinel lymph node in breast cancer.

Immunohistochemistry of histologically negative axillary lymph nodes in breast-cancer patients resulted in upstaging of the sentinel lymph node in eight (14%) of 52 patients. The resulting information altered clinical management in six of these patients. Thus, this technique may affect clinical decision-making in breast-cancer patients.

Randomized multicentre trial of filgrastim as an adjunct to combination chemotherapy for Hodgkin's disease. West of Scotland Lymphoma Group.

This study was intended to ascertain whether the adjunctive administration of filgrastim (r metHuG-CSF, Amgen) would influence the dose intensity of chemotherapy or the morbidity of myelosuppression in patients receiving MOPP or MOPP/EVAP hybrid chemotherapy for Hodgkin's disease. In a prospective randomized trial, two regimens for the treatment of Hodgkin's disease were compared. The substudy described here randomized patients receiving either regimen to receive filgrastim on the days when chemotherapy was not administered. During chemotherapy, parameters of myelosuppression were documented, including dose delays, the severity and duration of neutrophil and platelet nadirs, infective episodes, and resulting hospital admissions. In the MOPP arm, 13/25 eligible patients, and, in the MOPP/EVAP arm, 12/22 eligible patients, received filgrastim. The use of filgrastim made no statistically significant difference to the administered dose intensity for either MOPP (P = 0.57, 95% confidence interval (CI) 15-point increase to 8-point reduction) or MOPP/EVAP (P = 0.53; 95% CI 7-point increase to 11-point reduction). In patients receiving MOPP, filgrastim reduced the median duration of leucopenia (P = 0.007) and the severity of the white blood cell nadir (P = 0.036); however, no statistically significant effect (at the 5% level) was seen in platelet or haemoglobin nadirs, the number of days of in-patient hospitalization, the number of admissions for infective complications, the incidence, grade or duration of infections, or the incidence of febrile neutropenia. In patients receiving MOPP/EVAP, filgrastim had no significant effect on the duration or depth of leucopenia but was associated with a reduction in the median haemoglobin (P = 0.002) and platelet nadirs (P = 0.015). No effect on the above listed sequelae of myelosuppression was influenced by the administration of filgrastim. This study, although small, suggests that the routine use of filgrastim, aimed at influencing the administered dose intensity of conventional dose chemotherapy in Hodgkin's disease, is not warranted.

Clinical trials of nimodipine as a potential neuroprotector in ovarian cancer patients treated with cisplatin.

Our previous randomised trial in patients with advanced ovarian cancer indicated a significant response and survival advantage for those receiving high-dose (100 mg/m2) as compared with low-dose (50 mg/m2) cisplatin in combination with cyclophosphamide (750 mg/m2). However, this was accompanied by more toxicity; peripheral neuropathy was troublesome, with 32% of patients experiencing > or = WHO grade 2 at the cisplatin dose of 100 mg/m2. Nimodipine is a calcium-channel antagonist that has provided protection from cisplatin-induced neurotoxicity in a rat model system. We performed a pilot study in 50 patients that demonstrated the feasibility of co-administration of nimodipine in a chronic oral dosing schedule with cisplatin-based chemotherapy in an open-label non-randomised trial. This led us to initiate a double-blind, placebo-controlled, randomised trial in patients with ovarian cancer, which was prematurely discontinued because of problems with nausea and vomiting, leading to poor patient compliance, that were not predicted by the pilot study. These studies did not demonstrate a neuroprotective effect for nimodipine. The primary efficacy variable, i.e, the neurotoxicity score at the end of treatment, gave a significantly lower mean for placebo patients than for nimodipine patients. This report details our experience and discusses the reasons for premature termination of the randomised trial.

Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

PURPOSE: In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS: After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS: The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION: Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Management of cyclophosphamide-induced emesis over repeat courses.

This paper describes the only published study to date which prospectively evaluates the efficacy of a 5-HT3 receptor antagonist over repeated courses of cyclophosphamide chemotherapy. The combination of ondansetron and dexamethasone was significantly superior to metoclopramide and dexamethasone over 6 courses of chemotherapy given for the treatment of breast cancer. Importantly, patients given ondansetron benefited from a superior quality of life over the six courses of treatment. A Markov chain statistical model has been applied to these data. This model assumes that the results over subsequent courses is dependent on the efficacy of the anti-emetic therapy and the results obtained during the previous course of chemotherapy. This model successfully predicts the actual results obtained in the clinical study. Using this model it is possible to hypothesise on the results obtained following different treatment strategies. These data emphasise that it is important to give optimal anti-emetic therapy from the first course of chemotherapy as this will facilitate good control during subsequent courses.

A pilot study of combination therapy with interferon-alpha-2a and 5-fluorouracil in metastatic carcinoid and malignant endocrine pancreatic tumours.

BACKGROUND: In view of the encouraging single agent response rates to interferon and 5-fluorouracil (5-FU) in malignant carcinoid and endocrine pancreatic tumours and the theoretical benefits of combination therapy with 5-FU and interferon in other tumours a study was designed to look at the feasibility of this combination, given for 12 months, in these tumours. PATIENTS AND METHODS: Patients were treated with 5-FU 750 mg/m2 by intravenous bolus every week and 3 Mega Units of recombinant interferon-alpha-2a subcutaneously 3 times per week increasing, as tolerated, to 6 then 9 MU. Fifteen patients were entered into the study. RESULTS: One patient died suddenly of an unrelated illness and is not assessed. None of the remaining 14 patients had radiological evidence of response to treatment, although 6 had stable disease lasting for 7 to 64 weeks (median 40 weeks). Two patients did have biochemical evidence of a response, i.e., a 50% reduction in baseline urinary 5HIAA for 26 and 52 weeks. Treatment toxicity was significant. Six patients stopped treatment prematurely because of either nausea and/or diarrhoea. Overall treatment duration ranged from 4 to 64 weeks (median 7.5 weeks). CONCLUSION: Overall we found the treatment to be disappointing in terms of tolerance and response rate and do not recommend its use in malignant carcinoid or endocrine pancreatic tumours.

Bioavailability of subcutaneous 5-fluorouracil: a case report.

The optimal schedule for the administration of 5-fluorouracil (5-FU) in the management of advanced colorectal cancer remains to be determined. It has been suggested that this drug may be given by the subcutaneous route and that following a short infusion the bioavailability is similar to that observed after intravenous administration. We report the results we obtained in a patient treated with an intravenous bolus of 5-FU followed by a 22-h subcutaneous infusion. In this patient the bioavailability of 5-FU given by subcutaneous infusion was 0.94. The steady-state plasma levels of 5-FU reached during subcutaneous infusion were comparable with those achieved during intravenous infusion. Following four cycles of subcutaneous therapy, painless blistering was noted at the infusion sites, which healed following the cessation of subcutaneous therapy. Further studies are required to evaluate this route of therapy as an alternative to protracted intravenous therapy. The main dose-limiting side effect appears to the local skin toxicity.

Pamidronate infusions as single-agent therapy for bone metastases: a phase II trial in patients with breast cancer.

Pamidronate is a potent biphosphonate which modulates tumour-induced osteolysis (TIO) by inhibiting osteoclast-mediated bone resorption. In a phase II trial, 69 breast cancer patients with symptomatic progressive bone metastases were given infusions of pamidronate 60 mg over 1 or 4 h every 2 weeks for a maximum of 13 infusions or until progressive disease (PD) at any site. No other systemic anticancer therapy was allowed. Pain was measured using a visual analogue scale, mobility using a detailed eight-point questionnaire and analgesic intake using a six-point scale. Improvements in pain, mobility and analgesic scores occurred in 61, 50 and 30% of patients, respectively, with 33, 21 and 16% achieving a 40% improvement for > or = 8 weeks. At trial discontinuation, baseline levels of pain and mobility had improved by 27% (P = 0.001) and 20% (P = 0.004), respectively, despite a one category reduction in analgesic intake in 27% of patients. Using this relatively high dose of pamidronate, symptomatic response was independent of the number of bone metastases and also of infusion rate. The infusions were well tolerated with no major toxicities reported. Pamidronate infusions provide useful palliation for breast cancer patients with symptomatic bone metastases.