The feasibility of classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for pre- and post-menopausal node-positive breast cancer patients in a Belgian multicentric trial: a study of consistency in relative dose intensity (RDI) and cumulative doses across institutions.

BACKGROUND: Classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) including oral cyclophosphamide is still considered an important adjuvant chemotherapy regimen in patients with early breast cancer (BC). Concern has been raised regarding the feasibility of this regimen, especially in postmenopausal patients. PATIENTS AND METHODS: 254 pre- and post-menopausal node-positive BC patients aged < or = 70 years received six cycles of CMF in the context of a Belgian multicentric phase III trial of adjuvant chemotherapy. CMF dose and schedule were as follows: cyclophosphamide 100 mg/m2 p.o. on days 1 to 14, methotrexate 40 mg/m2 intravenously (i.v.) on days 1 and 8, 5-fluorouracil 600 mg/ml i.v. on days 1 and 8; cycles q. 28 days. The relative dose intensity (RDI) was calculated as the ratio between the delivered DI and the planned DI. We also analysed the RDI in two subgroups of patients with age > or = 50 years or < 50 years. RESULTS: Overall, the percentage of patients ending the six cycles of the planned CMF regimen was 90%. The mean RDI achieved in the population of 254 patients was 90% (range 8% to 129%). The subgroup analysis of patients aged > or = 50 years and < 50 years showed that 81% and 76% of patients, respectively, received > or = 80% of the planned chemotherapy dose intensity (P = 0.33). No statistically significant difference was found between the percentage of patients who received a RDI < 80% and the participating institutions (P = 0.50). CONCLUSIONS: The classical CMF regimen was a feasible regimen in the context of a multicentric trial, in which academic institutions as well as community hospitals participated. No substantial differences in RDI and cumulative doses were found in relation to a patient's age and the participating institution.

Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicin in the adjuvant treatment of node positive breast cancer: results of a feasibility study.

BACKGROUND: Doxorubicin (A) and Docetaxel (T) are amongst the most active agents in breast cancer treatment. The impact of drug sequencing is an issue still under evaluation. OBJECTIVE: To evaluate the feasibility and tolerability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed. METHODS: The study included patients pts aged < or = 70 years, with operable node positive breast cancer. Two consecutive groups of patients received one of the following regimens: 1) Sequential A-->T-->CMF: Doxorubicin 75 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2) Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14 + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks). An analysis of treatment administration and toxicity was performed for the first six cycles of CT, in the two treatment groups. RESULTS: Group 1 with 20 patients and group 2 with 14 patients were balanced in terms of patient and tumour characteristics. There was one early treatment discontinuation in each group due to toxicity (one allergic and one skin reaction to docetaxel). Median relative dose intensity was 100% for both drugs in both groups. The most relevant side effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue 80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups. CONCLUSIONS: 1) Both sequences were estimated feasible due to the optimal treatment administration and limited incidence of G3-G4 side effects. 2) The concomitant use of lenograstin might partially explain the reported incidence of myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable regimen due to the limited number of patients.

Carcinomatous meningitis as a clinical manifestation of pancreatic carcinoma.

Carcinomatous meningitis (CM) is clinically less common than brain metastasis or spinal cord compression, having dire consequences for both the quality of life and the overall survival of patients with solid tumors. It occurs in about 5% of all adult cancer patients, but autopsies may double this number. If leukemia and lymphoma are excluded, most cases are due to breast cancer, lung cancer and melanoma. In this report, we describe a 49-year-old male patient with metastatic pancreatic adenocarcinoma who developed carcinomatous meningitis. To our knowledge, this is only the second case of carcinomatous meningitis secondary to a pancreatic carcinoma described so far.

Phase II trial of paclitaxel and ifosfamide as a salvage treatment in metastatic breast cancer.

PURPOSE: Treatment results in patients failing first-line chemotherapy in metastatic breast cancer (MBC) are still unsatisfactory, with patients exhibiting poor responses to salvage therapy and a short overall survival. Both paclitaxel and ifosfamide are able to produce objective tumor responses in this disease. Therefore, the antitumor effects and toxicity of their combined use could be worthwhile studying in patients progressing after doxorubicin-containing combinations. PATIENTS AND METHODS: This Phase II trial of paclitaxel/ifosfamide included patients with bi-dimensionally measurable metastatic breast cancer in second or third relapse, following anthracycline-containing regimens; ECOG PS < 2, and adequate hepatic, cardiac, renal, and hematological functions. Paclitaxel 175 mg/m2 was given on day 1, in a 3-hour infusion with appropriate antiallergic pre-medication; while ifosfamide 1.8 g/m2 was given on days 2, 3, 4 with mesna 360 mg/m2 i.v., 15 minutes before and 4 hours after ifosfamide administration, and 720 mg/m2 P.O. 8 hours later at home, also on days 2, 3, 4. The cycles were repeated every 21 days, on an outpatient basis. RESULTS: Twenty-four patients were accrued for the study and 23 were considered eligible for the evaluation of toxicity and response. Previous chemotherapy included: CMF/FAC (16 cases); CMF plus mitoxantrone/FAC/cisplatin, vinblastine, mitomycin C (2 cases): and FAC/mitomycin C, vinblastine, and etoposide (5 cases). There were 11 (48%) objective responses (95% C.I.:27-69%), including 2 (9%) CR and 9 (39%) PR (95% C.I.:0-21% and 19-61%, respectively). Five (22%) patients attained disease stabilization. Median response duration was 7+ months (range 4 to 20+), and the median overall survival was 12 months (range 4-23+). The regimen was well tolerated. WHO nausea/ vomiting grades 1-2, alopecia grade 3, and neutropenia grades 1-2 were seen in most patients. Four patients experienced mild neuropathy, while it was grade 3 in 1 case. Seven patients had grade 3 neutropenia. In addition, grade 4 neutropenia associated with fever was documented in other 4 cases. No hypersensitivity reactions were seen. One case of reversible tachycardia after drug administration was seen. Myalgia grades 1-2 was also reported in some patients. CONCLUSION: These results suggest that the present regimen has significant activity in heavily pretreated patients with a MBC, with a manageable toxicity profile. Further trials exploiting the above mentioned drug combination are warranted.

A phase II study of doxorubicin/paclitaxel plus G-CSF for metastatic breast cancer.

This phase II trial was conducted to evaluate the percentage of objective responses and the toxicity profile of combination doxorubicin (Adriamycin) and paclitaxel (Taxol) with granulocyte colony-stimulating factor as first-line therapy for patients with metastatic breast cancer (MBC) not previously exposed to anthracycline-containing regimens. Patients with measurable, visceral-dominant MBC and a performance status of 0 to 2 were included in the study. Doxorubicin 60 mg/m2 was administered as a short intravenous infusion, followed by paclitaxel 250 mg/m2 as a 3-hour intravenous infusion on day 1. Granulocyte colony-stimulating factor 5 micrograms/kg/d was given prophylactically as a subcutaneous injection from day 2 until granulocyte recovery to > or = 1,500/mm3. Treatment was repeated every 21 days for a maximum of six courses. Dose reductions (to doxorubicin 50 mg/m2 and paclitaxel 175 mg/m2) and/or treatment delay were applied in case of severe toxicity. All 25 women who entered were evaluable for response and toxicity. The main grade 3/4 toxicities observed were leukopenia, thrombocytopenia, and mucositis. Alopecia occurred in all patients. No clinically relevant cardiovascular toxicity was observed. Severe myelosuppression and/or mucositis necessitated dose reductions at courses 2 or 3 in all but one patient. The complete response rate was 28%, and the partial response rate was 52% for an overall objective response rate of 80%. Median progression-free survival for complete responders was 11 months (range, 3 to 24 months), while the progression-free survival was 7+ months (range 2 to 14+ months) for partial responders and 5 months (range, 3 to 9 months) for nonresponders. This combination produces a high objective response rate in women with MBC, but dose reductions were necessary in almost all cases. Toxicity was manageable after dose reduction, allowing patients to be re-treated for two to six courses without life-threatening toxicity or toxic deaths. Unfortunately, the duration of response was limited even among complete responders. Further trials of this combination in patients with MBC should explore improvements in this study regimen.