Drug concentrations in axillary lymph nodes after lymphatic chemotherapy on patients with breast cancer

From June 2002 to August 2003 a total of 60 female patients with breast carcinoma confirmed by preoperative puncture-biopsy were enrolled in this study. The ages of patients ranged from 35 to 71 years (mean 49.2 years). The pathological diagnoses were as follows: ductal (n = 28), lobular (n = 18), medullary (n = 6), mucinous (n = 4), tubular (n = 3) and papillary (n = 1) carcinoma, respectively. According to the TNM classification (AJCC Cancer Staging Manual, 6th edition, 2002), 11 patients fell into the T₁ category, 38 into T₂, 8 into T₃ and 3 into T₄. Axillary lymph node metastases were present in 23 patients; of these, 17 were classified as N1, 5 as N2 and 1 as N3. Distant metastases occurred in four patients. Clinical grades consisted of grade I (n = 9), grade II (n = 40), grade III (n = 7), and grade IV (n = 4). Locations of tumours were as follows: subnipple (n = 5), outer-upper (n = 21), outer-lower (n = 14), inner-upper (n = 11) and inner-lower (n = 9) field. The inclusion criteria included the following: World Health Organization status of 0 or 1, without previous chemotherapy or radiation therapy, white blood cell count greater than 4000/μl and platelet count greater than 100,000/μl, no abnormality of cardiac, renal or liver function. The patients who met these criteria were divided into two groups in accordance with a prospectively generated randomization schedule, with 30 patients in each group, to receive either LC or VC as preoperative adjuvant treatment. The study protocol was approved by our institutional review board as being in accordance with the Declaration of Helsinki. Informed consent was obtained from every patient before enrolment.

Activated carbon granules (CHR-30) were ground in a ball-mill and sifted with a 100-mesh sieve. The 100-mesh passing fraction, 81% of which was smaller than 40 μm, was used for this preparation as activated carbon particles. After the moisture had been removed from the activated carbon particles by dry heating at 120°C for 2 hours, 375 mg of activated carbon particles was sealed in a glass tube, which was sterilized under two atmospheres of pressure for 10 minutes and stored in a refrigerator. Just before use, 100 mg of carboplatin dissolved in 20 ml of normal saline was added to the activated carbon particles. The mixture was shaken for 10 minutes to allow sufficient adsorption of carboplatin on the activated carbon particles, resulting in CP-CH [6].

Patients in the LC group received a subcutaneous injection of 4 ml of CP-CH, containing 20 mg of carboplatin, adjacent to the primary tumour. The VC group received an intravenous injection of 4 ml of CP-Sol containing 20 mg of carboplatin. Modified radical mammectomies were performed 1, 12, 24, 36 and 48 hours later on 12 patients, with 6 from each group each time. Axillary lymph nodes were excised entirely, one of which was picked at random and split into two parts: one part was sent for platinum examination, and the remaining part and the rest of the lymph nodes were sent for histopathological observation. The lymph node for platinum examination was cut to a fragment weighing 200 mg and placed in a 5 ml screw-capped tube. The fragment was left to stand overnight with 4 ml of 10% hydrochloric acid and 70% nitric acid (1:4, by volume). The following day, tissue was digested for 2 hours at 90°C in an electric frying pan positioned in a fume hood. The solubilized tissue was dried and mixed with 0.5 ml of Milli-Q water. The solution was subjected to graphite-furnace Zeeman atomic absorption spectrometry. Platinum analysis was performed as described previously [7]. The concentration of carboplatin was determined by multiplying the concentration of platinum by 1.903.

Concentrations are shown as means ± SD. Results were tested for significant differences by Fisher's test and Student's t-test. P < 0.05 was considered to indicate statistical significance.