Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

[Phase I study of SM-5887, a new anthracycline derivative].

SM-5887, a new totally synthetic anthracycline derivative, was studied in a phase I setting. Twenty-nine evaluable courses of treatment were conducted in groups at doses increasing from 10 to 130 mg/m2. At 130 mg/m2 the median lowest WBC count was 0.7 x 10(3)/mm3 (range 0.3-1.8) and the median lowest platelet count was 57 x 10(3)/mm3 (range 4-176). Nonhematological side effects were mild gastrointestinal symptoms and hair loss. The recommended dose and schedule for a phase II setting is 100 mg/m2 every 3 weeks.

[Combined chemotherapy with cisplatin and aclarubicin hydrochloride for metastatic brain tumors].

Thirteen patients with metastatic brain tumors were treated by combined chemotherapy with cisplatin and aclarubicin hydrochloride. Initial response to this therapy was evaluated by the changes of tumor size on CT scan and clinical state during and after the treatment. The side effects and the causes of death were also studied. Nine cases demonstrated complete remission and 3 cases revealed partial response on CT scan. In short, over all response rate was 92%. Clinical state evaluated by Karnofsky scale was improved in 9 out of 13 cases. As the side effects, there were mild myelosuppression, nausea and vomiting, which didn't persist for a long time. The cause of death was mainly due to recurrence of primary lesion. The tissue concentration of aclarubicin hydrochloride was measured in 6 patients, of which mean value was 0.558 microgram/g at 15 min. The concentration was thought high enough to kill tumor cells.

[Chemotherapy combining vindesine, thiotepa and methotrexate in metastatic breast cancer after failure of a combination containing anthracycline. Results of a prospective phase II trial]. / Chimiothérapie associant vindésine, thiotépa et méthotrexate dans les cancers du sein métastatiques après échec d'une combinaison incluant une anthracycline. Résultats d'un essai phase ii prospectif.

Twenty-six patients with metastatic breast cancer where treated, after failure of a first line chemotherapy including an anthracycline, with a second line combination of vindesine, methotrexate and thiotepa. Overall tolerance of this treatment was good. There were one complete response and two partial responses. The authors conclude that this treatment has a marginal activity.

[Pharmacokinetic study of aclarubicin. The pharmacokinetics of the preparation and its biologically active metabolites in the blood of rats]. / Farmakokineticheskoe izuchenie aklarubitsina. Farmakokinetika preparata i ego biologicheski aktivnykh metabolitov v krovi krys.

Blood pharmacokinetics of the antitumor antibiotic aclarubicin and its metabolites was studied in rats with high performance liquid chromatography. The drug was administered intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. Aclarubicin pharmacokinetics was shown to be nonlinear. However, within every dose level it obeyed a two-compartment model. The nonlinearity could be due to saturation of aclarubicin binding to blood plasma proteins. The blood concentrations of metabolites MA144 N1 and MA144 T1 were close and after 12-18 hours exceeded those of unchanged aclarubicin. The half-lives of aclarubicin and its metabolites ranged from 16 to 21 hours. The MA144 T1 content was not significant. Following oral administration aclarubicin was rapidly absorbed and its bioavailability amounted to 35 per cent. Total bioavailability of aclarubicin, MA144 N1 and MA144 T1 was equal to 89 per cent. This enabled to consider the oral route of aclarubicin administration promising in tumor therapy.

[Pharmacokinetic study of aclarubicin. The distribution of the preparation and its biologically active metabolites in rat tissues]. / Farmakokineticheskoe izuchenie aklarubitsina. Raspredelenie preparata i ego biologicheski aktivnykh metabolitov v tkaniakh krys.

Tissue pharmacokinetics of aclarubicin and its active metabolites was studied with high performance liquid chromatography. The drug was administered to rats intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. With both the administration routes the highest concentrations of the drug and its metabolites were attained in the lymph nodes. Then followed the spleen and lungs. The lowest content of the drug was detected in the heart. The total values of the areas under the concentration/time curves for aclarubicin and its metabolites in the tissues of the heart, lungs, lymph nodes and spleen after oral administration were respectively 2, 3, 4 and 7 times lower than those after the drug intravenous administration in the same dose. The concentrations of the active metabolites MA144N1 and MA144T1 exceeded those of aclarubicin and were detected in the tissues within a longer period as compared to the unchanged drug. With repeated administration preferential accumulation of the metabolites in the tissues and their increased contribution to the aclarubicin antitumor effect could be suspected.

[A case of Ewing's sarcoma treated successfully by combination chemotherapy consisting of high-dose methotrexate, aclacinomycin-A and vindesine].

A 22-year-old man was admitted to Kyushu University Hospital because of high fever, and pain in the right foot and back. An X-ray examination revealed an osteolytic lesion on the 5th metatarsal bone of the right foot. Paraplegia and disturbance of bladder function occurred and compression of the spinal cord between T3 and L5 was found by myelography. An extradural tumor was removed by emergent laminectomy, and a histological examination of the tumor showed aggregations of small round cells, which suggested Ewing's sarcoma. Although T-9 protocol was started with initial effect, the tumor recurred during the therapy. The patient was then treated with HD-MTX, ACR and VDS, which induced a clinical improvement for 4 months without maintenance therapy. This result showed that HD-MTX, ACR and VDS warrant further consideration for the treatment of refractory Ewing's sarcoma.

[The effect of combined chemotherapy with UFT, cis-platinum and aclarubicin in metastatic brain tumors].

Thirteen patients with metastatic brain tumors were treated with two different chemotherapy regimens. Six patients were treated with three antitumor drugs, UFT, CDDP and ACR (Group A) and the other seven patients were treated with two antitumor drugs, CDDP and ACR (Group B). Initial response to each therapy was compared with the changes in tumor size on CT scan and clinical state before and after treatment. Five cases in Group A demonstrated complete remission and one case revealed partial response on CT scan. The residual tumor on CT scan at one month in one case of partial response also completely disappeared after three months. It was thought that there might have been an effect of UFT in this case. Four cases in Group B showed complete remission and three cases revealed partial response on CT scan. However, the CT findings in the three cases of partial response were unchanged on follow-up CT scan. Clinical state evaluated by Karnofsky scale did not deteriorate in Group A, while three cases showed a deteriorated Karnofsky scale in Group B. As side effects, there were mild myelosuppression, nausea and vomiting in both Groups, which did not persist for a long time. The cause of death in both Groups was mainly recurrence of the primary lesion or metastasis to other organs. It was thought that the effect in Group A was better than that in Group B as a result of these findings. The tissue concentration of ACR was measured in six patients, and the mean value was 0.558 micrograms/g at 15 min. This concentration was thought high enough to kill tumor cells.

[Our experience with combined intravesical instillation therapy of superficial bladder tumor using Aclacinomycin-A (ACM) and cytosine arabinoside (CA)].

Thirteen patients with recurrent superficial bladder tumors were treated by combined intravesical instillation of Aclacinomycin-A (ACM) and cytosine arabinoside (CA). Prophylactic effects of this combined instillation therapy were studied in 7 patients. A solution of 200 micrograms/ml of ACM and 600 micrograms/ml of CA was instilled into the bladder. The instillation aimed for treatment was carried out once a week until ten treatments had been given. Complete response was attained in 2 patients and partial response in 3 patients, but tumor size increased by more than 50% in 6 of the 13 patients. No change was observed in the remaining 2 patients. Recurrence of the tumors was observed in 3 of the 7 patients who were treated by this prophylactic combined instillation therapy. Local side effects such as bladder irritability were found in 2 of the 20 patients. No systemic side effects were noted in any patients. Although the side effects were reduced, we were not satisfied with the results of this therapy.

[Treatment of advanced bladder cancer with intra-arterial infusion of cisplatinum (CDDP) and aclacinomycin (ACR), combined with angiotensin II].

Ten patients with advanced bladder cancer were treated with intra-arterial infusion therapy. The patients consisted of nine males and one female between 55 and 82 years old (median: 70 years). In all patients, cisplatinum (CDDP) (2 mg/kg), aclacinomycin (ACR) (0.5 mg/kg) and Angiotensin II (25 mg) were infused via the internal iliac artery for a period of about 30 minutes. Seven patients also received X-ray therapy with a linac. The efficacy of this therapy was assessed by computed tomographic scanning, sonography and cystoscopy. As a result of this assessment, 2 patients were rated complete response "(CR)", 6 partial response (PR) (showing 50% or more reduction in the lesion) and 2 no change "(NC)". To compare the efficacy of this therapy for two histopathologically defined groups of patients (patients with grades 2 and 3 cancer), one patient was rated "CR", four "PR" and two "NC" in the grade 3 group (total 7 patients), while one was rated "CR" and two "PR", in the grade 2 group (total 3 patients). In effective cases, pollakiuria and miction pain disappeared shortly following intra-arterial infusion therapy. As for side effects of the therapy, mild nausea or vomiting was observed in all patients, while leukopenia was noted in one patient.

[Clinical trials of combination chemotherapy using cis-platinum with aclarubicin in intracranial rhabdomyosarcoma].

Combination chemotherapy of Cis-platinum with Aclarubicin was performed in patients with intracranial alveolar rhabdomyosarcoma. These patients were treated with Cis-platinum (20 mg/day) and Aclarubicin (20 mg/day) for 5 days. After two trials with about a four-week interval, complete tumor regression on CT scan was observed. Mild gastrointestinal toxicity was observed in these patients but the symptoms were transient and soon disappeared. No other side effects appeared, on or after treatment. This result demonstrated that combination chemotherapy of Cis-platinum and Aclarubicin is an effective regimen for remission induction chemotherapy in patients with intracranial sarcoma.

Alfa interferon: combinations with other antineoplastic modalities.

Early laboratory work demonstrated synergism from the combination of various cytotoxic agents and alfa interferon against various cell lines. In conjunction with anecdotal clinical reports of this synergism, multiple clinical trials were initiated to determine the tolerance and toxicity of the alfa interferons in conjunction with other antineoplastic agents/modalities. Phase I-II studies have been completed with alfa interferon and melphalan/prednisone, vincristine, vinblastine, etoposide (VP-16), cyclophosphamide, and radiation. In general, it may be stated that the toxicities are nonoverlapping and not unexpected. The tolerable doses of the interferons (IFNs) have generally been low. The future of research with interferon may be divided into three areas: Efforts must be made to determine how best to translate the in vitro synergy into clinically meaningful terms; in order to exploit the fullest potential of IFN, research is moving toward using this agent earlier in disease either as an adjuvant after tumor debulking or after initial diagnosis; the medical community must rethink the natural history of some diseases, because the fullest potential of the biologic agents will most likely manifest itself when these agents are used together.

Aclacinomycin A. Phase II evaluation in bronchogenic squamous-cell carcinoma.

Aclacinomycin A (ACLA-A) was administered to 22 patients with metastatic measurable bronchogenic squamous-cell carcinoma in a Phase II trial of the drug. Sixteen patients were fully assessable for response and toxicity. The initial dose of ACLA-A was 85 mg/m2 weekly for 4 consecutive weeks; however, due to severe myelosuppression, the weekly dose was reduced to 65 mg/m2. Fifteen patients were previously untreated. Toxicity was primarily hematological. Complete or partial responses were not observed on this treatment schedule. ACLA-A administered on this schedule lacks therapeutic efficacy in the treatment of patients with advanced bronchogenic squamous-cell carcinoma.

Aclacinomycin A. Phase II evaluation in advanced soft tissue sarcoma.

Aclacinomycin A (ACLA-A), an anthracycline antibiotic, was administered in a Phase II study to 20 patients with advanced, measurable soft tissue sarcomas. The dose schedule consisted of 85 mg/m2 intravenous ACLA-A given weekly for 4 weeks followed by a 2-week rest. Because of severe myelosuppression in the initial patients, the weekly dose was reduced to 65 mg/m2. Seventeen patients were fully evaluable for toxicity and response to the drug. Complete or partial responses were not identified. Toxicity was primarily hematological. ACLA-A administered in the above schedule demonstrated no therapeutic efficacy in patients with advanced soft tissue sarcomas.

[Cancer chemotherapy combined with a calcium antagonist in patients with hematologic malignancies and solid tumors resistant to standard chemotherapy].

Cancer chemotherapy combined with calcium-channel blockers was administered to seventeen evaluable patients with hematologic malignancy and solid tumor who became resistant to standard chemotherapies between November 1981 and June 1986 in Saitama Cancer Center. Nicardipine and diltiazem were used as the calcium-channel blockers, which were given orally or intravenously. Adriamycin and/or vinca alkaloids were mainly used as a cancer chemotherapy. Partial remission was attained in 3 of 6 patients with malignant lymphoma. Remission was attained in 2 of 7 patients with acute leukemia including acute transformation of chronic myelogenous leukemia (CML/BC), one complete remission with acute lymphocytic leukemia and one cytoreductive effect with CML/BC. One partial response and one minor response were obtained among 4 patients with solid tumor. The remission of these responders was of short duration. The most serious side effect caused by calcium-channel blockers was hypotension, which was dose-limiting and induced oliguria in 6 of 23 courses. In conclusion, the clinical impression obtained with regard to the effectiveness against chemotherapy-resistant malignancies of cancer chemotherapy combined with calcium-channel blockers was not good even though the overall remission rate was 41%.

[Treatment of a case of childhood acute non-lymphocytic leukemia (ANLL) using high-dose cytosine arabinoside for intensification of early therapy].

A 12-year-old girl with acute non-lymphocytic leukemia was treated with a protocol involving high-dose cytosine arabinoside (Ara-C) for intensification of early therapy. The patient, who had been revealed to have CNS infiltration on admission, achieved complete remission after receiving ACMA/BHAC combination and intrathecal MTX. As an early intensification treatment, ID/HD Ara-C was safely and effectively administered; this consisted of ADR (45 mg/m2 iv) Day 1, intermediate-dose Ara-C (0.5 g/m2, 1-h drip, q. 12 h) Days 2-4, and high-dose Ara-C (3 g/m2, 3-h drip, q. 12 h) Days 10-11, followed by L-asp (6,000 U/m2, im) on Day 12. Ten months later, the patient has been in continuous complete remission. High-dose Ara-C should be included with caution as an early intensification of treatment to improve the therapeutic results of childhood ANLL.