1/7. A unique experience with human pre-immune (12 weeks) and hypo-immune (16 weeks) fetal thymus transplant in a vascular subcutaneous axillary fold in patients with advanced cancer: a report of two cases.BACKGROUND: The successful development of fetal cell/tissue transplantation in adults has resulted in the possibility of eventual therapeutic solutions with a variety of intractable diseases. umbilical cord whole blood transplantation appears to be safe in the adult system. In severe forms of digeorge syndrome, cultured thymus transplant can help in the reconstitution of the immune condition of the host. Successful fetal tissue transplant in adults has raised the hope of future effective gene transplant and its manipulation prospects to combat many diseases including hemopathies, inborn errors of metabolism, immunodeficiencies and even cancer and AIDS. MATERIALS AND METHOD: Two cases of advanced cancer were treated with fetal (pre-immune 12 weeks and hypo-immune 16 weeks) thymus transplants in subcutaneous vascular axillary folds, which were removed after one month. Thymuses were collected from consenting mothers undergoing hysterotomy and ligation. RESULTS AND ANALYSIS: Patient I was suffering from non-Hodgkins lymphoma (Ann Arbor Stage IV) and was receiving cyclophosphomide, doxorubicin, vincristine and prednisolone after a course of radiotherapy; she developed leucopenia (2.400/cmm), which improved after receiving a 16-week human fetal thymic graft. The leucopenia was eventually over-corrected and the leucocyte count reached 44,000/cmm within a month, which was reversed after the thymus was taken out. histology of the excised thymic graft showed growth and proliferation without any graft vs. host (GVH) reaction. Patient 2 was suffering from breast duct carcinoma (T4, N2, M0,) with estrogen, progesterone, and epidermal growth factor negative status, and was treated with modified radical mastectomy and axillary clearance followed by chemotherapy with cyclophosphomide, methotrexate and 5-fluorouracil for six cycles. She also received a 12-week-old human fetal thymus at the contra-lateral axilla which was removed after one month. In this case the peripheral leucocyte count did not show appreciable variation as in the first case. However, histology of the excised thymic graft showed growth and proliferation with an appearance of Hassel's corpuscles. CONCLUSION: Pre-immune and hypo-immune human fetal thymic transplant is not rejected in patients suffering from advanced cancer within one month (observation period). Thymic lymphocyte shedding in the correction of leucopenia in the background of non-Hodgkin's lymphoma may have many therapeutic implications.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/7. Investigation into the usefulness and adverse events of CDDP, 5-fU and dl-leucovorin (PFL-therapy) for advanced colorectal cancer.Biochemical modulation of 5-fluorouracil (5-FU) has been verified the evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. We investigated the therapeutic and adverse drug reaction of intensive chemotherapy using cisplatin (CDDP), 5-FU and dl-leucovorin (LV) (PFL-therapy), which may be producing dual biochemical modulation effect of 5-FU for advanced colorectal carcinoma. Administration schedule was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days. This regimen was repeated at 3-week intervals in hospital. Sixteen patients were enrolled in this study, most of whom had a history of previous chemotherapy as adjuvant treatment, and the response rate was 25%, with four patients having "partial response" and eight "no change". In respect to performance status, 46% of patients who completed the protocol were markedly improved in spite of their poor performance status before treatment. Moreover, when patients were classified into two groups based on changes of the serum level of CEA, "responder in CEA level" showed better prognosis than "non-responder in CEA level". Major toxicities were nausea, hyperglycemia and neutropenia. Three patients experienced Grade 4 hematological side effect, but these complications resolved quickly in all patients except for one patient. PFL-therapy is effective for advanced colorectal cancer with large tumor burden and showed the same prognostic result as the American and European trials in spite of smaller number of treatment cycles and a history of previous chemotherapy. We will be able to demonstrate the usefulness of this regimen for Japanese patients with advanced colorectal cancers after adding new cases to the present report.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
3/7. Successful combination therapy with trastuzumab and paclitaxel for adriamycin- and docetaxel-resistant inflammatory breast cancer.We present a case of adriamycin-and docetaxel-resistant inflammatory breast cancer (IBC) in which partial response was achieved with combination therapy using trastuzumab and paclitaxel. A 48-year old woman noticed a lump in her right breast. She was diagnosed with IBC and the disease was staged as T4d N1 M0, stage III B. The patient was started on neoadjuvant chemotherapy with adriamycin (50 mg/m2) and docetaxel (60 mg/m2) administered every three weeks. Six courses were performed and the response was evaluated as no change. After one month, contralateral breast swelling indicated bilateral IBC. Bilatera1 mastectomy using the Halsted method was performed. The immunohistochemical results of the Hercep Test was strongly positive (3 ). After the mastectomy, right pleural effusion appeared, and cytological examination revealed the cells to be classV(adenocarcinoma). To treat the clinically advanced breast cancer, combination therapy with trastuzumab (initially 4 mg/kg followed by two or more cycles of 2 mg/kg) and paclitaxel (80 mg/m2) were given intravenously every week for eight cycles and then every two weeks thereafter. A total of 32 courses of therapy were performed, the pleural effusion completely disappeared and partial response was maintained for a duration of 482 days. The adverse reactions were mild, and it was possible for her to be treated as an outpatient with high quality of life. This report suggests that weekly combination therapy of trastuzumab and paclitaxel was useful for treatment of adriamycin-and docetaxel-resistant metastatic breast cancer.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |
4/7. Irinotecan therapy in a 12-year-old girl with recurrent brain stem glioma and without functional polymorphisms in UGT1A1 activity: case report.A 10-year-old girl was diagnosed with astrocytoma grade 2. Immuno-chemo-radiotherapy (interferon, ranimustine, and radiation), second-line chemotherapy (carboplatin and etoposide, 7 cycles) and third-line chemotherapy (ifosfamide, carboplatin, and etoposide) was given to treat progressive disease. Finally, irinotecan therapy was initiated and led to dramatic clinical improvement. Irinotecan is metabolized by carboxylesterase to form an active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) to yield its beta-glucuronide. The polymorphic UGT isoenzyme, UGT1A1 has genetic variants which decrease in SN-38 glucuronidating capacity and could help predict irinotecan-associated toxicity. The patient suffered excessive toxicity with low-dose irinotecan although no functional polymorphism in UGT1A1 was identified. We suggest that irinotecan offers an effective treatment option for children with recurrent brain stem glioma and other genetic variants except UGT1A1 may be a risk factor for irinotecan-induced toxicity.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
5/7. Clinical toxicity of combined modality treatment with nitrosourea derivatives for central nervous system tumors.Two nitrosourea compounds--1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)--have been used in the treatment of primary and metastatic brain tumors after operation and/or radiotherapy. Hematological and nonhematological toxicity were recorded in 272 patients treated between May 1973 and June 1978. BCNU was given to 135 patients (80 mg/m2 i.v. daily for 3 days) and CCNU was given to 137 patients (130 mg/m2 orally, single dose) every 8 weeks until progression of the primary disease process or for a total of 12 cycles. radiation therapy (5500 /- 500 rads in 6 to 7 weeks) was carried out after the first course of chemotherapy. BCNU and CCNU induced the same hematological and clinical toxicity. The bone marrow toxicity seemed to be dose-related, delayed, and cumulative. One case of acute nonlymphoblastic leukemia arising 2 months after the end of CCNU therapy is reported.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
6/7. Taxol in advanced, hormone-refractory carcinoma of the prostate. A phase II trial of the Eastern Cooperative Oncology Group.BACKGROUND. Recent clinical trials have documented activity for combinations of chemotherapeutic agents that target the microtubular apparatus in patients with hormone-refractory prostate cancer. Taxol has a novel antimicrotubular mechanism, acting by stabilizing polymerized tubulin. methods. Twenty-three patients with hormone-refractory prostate cancer and bidimensionally measurable disease were treated with Taxol by 24-hour continuous infusion at 135-170 mg/M2 every 21 days for a maximum of 6 cycles. RESULTS. Eighty-five courses of Taxol were administered to 23 patients. One patient (4.3%) experienced a partial response lasting 9 months, and four other patients with radiographically stable disease had minor reductions in the serum prostate-specific antigen (PSA) of 16-24%. Eleven patients (47.8%) had stable disease, and progressive disease developed in 9 patients (39.1%) during therapy. Median survival was 9 months. leukopenia was the dose-limiting toxicity with 13% of patients having Grade 3 and 61% having Grade 4 toxicity, and granulocytopenic fever developed in 26%. Three patients experienced sudden cardiovascular events while participating in the study, including one patient with a nonfatal, non-Q-wave myocardial infarction that occurred during a taxol infusion, and two patients who had sudden deaths 9 days and 30 days after receiving their last taxol dose, respectively. CONCLUSIONS. In the subset of patients with hormone-refractory prostate cancer and bidimensionally measurable disease, Taxol at this dosage has only minor activity.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
7/7. Antitumor activity of paclitaxel after failure of high-dose chemotherapy in a patient with late relapse of a non-seminomatous germ cell tumor.Although cisplatin-based chemotherapy considerably improved the clinical outcome of patients with metastatic germ cell tumors, approximately 20% of patients fail to achieve a durable remission to first-line treatment and require effective salvage treatment. As only 20-30% of patients can expect disease-free long-term survival after conventional salvage treatment, an increasing proportion of patients has been referred to high-dose chemotherapy with autologous stem cell rescue during recent years. However, high-dose chemotherapy still fails to cure a considerable number of patients, emphasizing the need to continue the search for new active drugs. We report here the case of a patient with late relapse of a non-seminomatous germ cell tumor who failed to respond to high-dose chemotherapy after heavy pretreatment with 11 cycles of cisplatin-based chemotherapy. The patient received paciltaxel for symptomatic disease with hepatic and pulmonary metastases, and attained a partial remission. Despite the heavy pretreatment, hematologic toxicity of paciltaxel was tolerable. As recent reports described responses to single-agent paciltaxel in a quarter of pretreated patients with germ cell tumors, further clinical trials seem justified to study the role of paciltaxel in combination regimens against this cancer type.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |