This study was undertaken to evaluate the clinical efficacy and toxicity of Nedaplatin (254-S) alone or combined for UFT for recurrent head and neck cancers in an outpatient setting. Thirty-two patients, previously treated, (30 men and 2 women, mean age 59 years, twenty one with loco-regional recurrence and 11 with distant metastasis, 29 with squamous cell carcinoma, 2 with adenocarcinoma and one with adenoid cystic carcinoma) were treated with Nedaplatin (254-S) alone or combined with UFT. The primary site was identified in the oropharynx in 8 patients, oral cavity in 7, larynx in 5, nasopharynx in 4, hypopharynx in 3, sinuses in one, parotid in one, and unknown primary in one patient. 254-S was administered at 80 mg/m2 by intravenous drip infusion. The 254-S administration was repeated at 4 week intervals, and in some patients was combined with daily oral administration of 400 mg of UFT-E (tegafur-uracil enterogranules). Twelve patients received 254-S alone and in 20 patients it was combined with UFT-E. The 254S administration ranged from one to 18 courses (mean of 5.7 courses). Grade 3-4 toxicities included leukopenia in 15.6%, anemia in 6.3% and thrombocytopenia in 9.4% of the patients. There was one death due to grade 4 leukopenic pneumonia. Four (12.5%) had a clinical complete and partial response. One-year and two-year overall survival rates were 35.6% and 30.5% for loco-regional recurrence, respectively. Ten of the eleven patients with distant metastasis died within six months and all patients were dead within 18 months, so a significant difference was observed in the overall survival rate between loco-regional recurrence and distant metastasis. Treatment with 254-S alone or combined UFT-E could be conducted in an outpatient setting and was able to improve the overall survival rate for recurrent head and neck cancer.

Our department recently began using paclitaxel in treating patients with breast cancer. Retrospective analysis was conducted to clarify its clinical usefulness. Forty-one patients with metastatic breast cancer were treated with paclitaxel between November 2000 and September 2002. Hospital records of the patients, except for one unsensored patient, were retrospectively reviewed. Characteristics of the patients were as follows: age, 36-81 Y (median, 56); 8 stage IV and 32 recurrent diseases; most frequent dominant site of metastasis was the liver (22 patients, 55%); number with previous chemotherapy was 0-5 (median, 2); anthracycline-based treatment and docetaxel treatment were previously performed in 21 (53%) and 15 (38%) patients, respectively; weekly dose of paclitaxel was 30-150 mg/body (median, 100); and total dose administered was 600-6, 480+ mg/body (median, 1,820). Objective response and clinical benefit rates were 35% and 80%, respectively. Median duration of response, time-to-progression and overall survival were 27+, 33+ and 41.5 weeks, respectively. Common adverse events were sensory neuropathy (45%) and nausea/vomiting (37.5%). Most were graded as 1 or 2. Various agents, such as hormonal agents and trastuzumab, were administered with paclitaxel in 26 patients (65%). No significant difference was observed in efficacy or toxicity among patients treated with paclitaxel alone or paclitaxel plus other agents. Paclitaxel seems to be a feasible, safe and active agent for patients with metastatic breast cancer.

The current status and measures for anticancer drug-induced lung injury and radiation pneumonia in cancer treatment were reviewed. Interstitial pneumonia induced by anticancer drugs is pathologically classified into the following: chronic interstitial pneumonia (CIP) or nonspecific interstitial pneumonia (NSIP), eosinophlic pneumonia (EP), bronchiolitis obliterans-organizing pneumonia (BOOP), diffuse alveolar damage (DAD), and hypersensitivity pneumonia (HP). In these pulmonary reactions to anticancer drugs, interstitial pneumonia manifested by DAD, which shows the acute or chronic clinical course, presents high mortality rates. Therefore, special care should be taken when DAD develops. Radiation pneumonia has two clinical phases, an acute phase of injury termed radiation pneumonitis, and a chronic phase of injuring termed lung fibrosis. It is usually confined to the irradiated area. On the other hand, sporadic radiation pneumonitis occurring outside the irradiated area has been reported besides classic radiation pneumonitis. Pathologically, it shows lymphocytic alveolitis or BOOP. Although radiation pneumonia has a good prognosis, mortality is rarely observed when lesion spreads outside the irradiated area.

A 73-year-old man presented with an ulcer and a subcutaneous nodule where he was receiving leuprorelin acetate injections to treat his prostatic carcinoma. Pathological findings of a skin biopsy showed many epithelioid granulomas with multinuclear giant cells, which contained small vacuoles. Recently, these lesions have been suggested to be caused by a type IV allergic response to the copolymer of lactic and glycolic acids used as a vehicle for drug administration. When urologists treat a prostatic adenocarcinoma with subcutaneous infusion of leuprorelin acetate, they should be aware of this potential side effect of the drug because the resulting granulomar formation may interfere with the effect of the drug. If patients suffer from subcutaneous nodules, urologists should consider changing the drug to an other type of luteinizing hormone-releasing hormone analogues such as goserelin acetate. This reaction to leuprorelin acetate has been reported in only seven cases including our case.

Based on presentations on the basic concepts and scientific rationale of anti-angiogenic approaches to cancer therapy and the possible applications in the area of prostate cancer, gastrointestinal cancer, lung cancer and breast cancer it is easy to conclude that development of anti-angiogenic approaches into clinical therapies is extremely challenging. It is now well established that cancer growth is increased by angiogenic factors and that inhibition of angiogenesis decreases growth and metastatic potential. Anti-angiogenic effect can be obtained through interference with multiple targets. Further development of new strategies involving such novel cancer therapies requires wide reaching development of translational research abilities. However, for moving new therapies into the clinic same rigorous criteria need to be applied as is done for traditional therapies. Angiogenesis appear to be a critical factor for development of prostate, gastric, lung and breast cancers. Development of new anti-angiogenic treatment modalities might become very important in these diseases. A critical requirement for the successful clinical development will be the development of imaging techniques that can help evaluate the effect on blood vessel functionality. Such surrogate markers of anti-angiogenic effect will be essential for optimising molecules and doses.

We report a case of advanced squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to oral chemotherapy with TS-1. The patient was an 89-year-old female with severe dementia. We carried out chemotherapy with TS-1 50 mg/day, without surgical treatment. The tumor disappeared clinically at 4 months after 3 courses of the TS-1 administration. Adverse drug reactions, including vomiting, leukopenia and thrombopenia, forced a stop of the administration of TS-1. Although she finally died of in senescence 2 months from the cease of administration, there was no recurrence of the cancer at the time.

Chemotherapy with TS-1 has recently become the first-line chemotherapy for recurrent and unresectable gastric cancer in Japan. Therefore, the establishment of a second-line chemotherapy is needed for cases that show resistance and aberrant effect to TS-1. In this study, 7 patients were treated with weekly administrations of paclitaxel after TS-1 treatment. We assessed the therapeutic effect and feasibility of chemotherapy with weekly administration of paclitaxel. Our results showed that weekly administration of paclitaxel could be a promising regimen as a second-line chemotherapy after TS-1.

The purpose of this study was to assess the safety of TS-1 when used as adjuvant chemotherapy after surgical resection of advanced stomach cancer.

A late phase II clinical study of S-1 against advanced or refractory breast cancer was done by 37 institutes in Japan. S-1 was administered twice daily at 80, 100 or 120 mg/body/day consecutively for 28 days followed by 14 days of rest (1 course). Eighty-three patients were enrolled and 81 were eligible for the study. The response ratio was 42.0% with 6 CR and 28 PR and its 95% confidence interval for the response was 31.1 to 53.5%. The median survival period was 910 days (95% confidence interval was 493-1, 083 days). The observed major adverse reactions (> or = grade 2) were as follows: hematological toxicities: leukopenia 21.0% (17/81), neutropenia 28.4% (23/81), erythropenia 4.9% (4/81); gastrointestinal toxicities: anorexia 9.9% (8/81), nausea and vomiting 12.3% (10/81), diarrhea 8.6% (7/81), stomatitis 1.2% (1/81), and fatigue 8.6% (7/81). The severe adverse reactions (> or = grade 3) were as follows; hematological toxicities: neutropenia 8.6% (7/81), anorexia 4.9% (4/81), fatigue 3.7% (3/81), nausea and vomiting 1.2% (1/81), diarrhea 1.2% (1/81), stomatitis 1.2% (1/81). Grade 4 adverse reactions (neutropenia and fatigue) were observed only in 1 patient. The ratio without hospitalization was 87.7%. These results strongly suggest the superior efficacy and safety of S-1 against patients suffering from advanced, refractory breast cancer. Therefore, S-1 may be a new therapeutic agent to prolong the survival period of breast cancer patients due to its high antitumor activity and low toxicity.

Cancer cells promote angiogenesis early in tumorigenesis because cancer cells require oxygen and nutrients for their survival they need to be supported by blood vessels. The angiogenic switch is driven by several proangiogenic factors, vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), basic fibroblast growth factor (bFGF) and others. These proangiogenic factors are released from not only cancer cells but also various stromal cells by various stimulations, mutations or inflammation. From our experimental results using human lung cancer cell lines, survival factors in each cancer cell line are different. This makes cancer therapy difficult. Various angiogenesis inhibitors have been developed to block tumor angiogenesis. However we need to think how and when to use angiogenesis inhibitors together with conventional chemotherapeutic agents.

A 29-year-old man with diffuse large B-cell lymphoma treated by radiotherapy for his relapsed lesion followed by 4 doses of weekly rituximab was admitted to our hospital with interstitial pneumonia. After steroid pulse therapy, he had contraction of the left visual field. He was diagnosed as having progressive outer retinal necrosis due to a varicella-zoster virus that was detected from the left vitreous sample. Systemic antiviral treatment failed to prevent rapid development of whole layer necrosis of the left retina. Vitrectomy with silicone oil tamponade saved his final visual acuity. This unusual event might be related to rituximab causing deterioration of humoral immunity.

A 79-year-old man was admitted because of consciousness disturbance on August 9, 2002. He had been diagnosed as having chronic myeloid leukemia in 1999, and since then, he had continued to take hydroxyurea (1500 mg/day) orally. On admission, his serum sodium concentration was as low as 119 mEq/L, while urinary sodium excretion was high. Based on the blood picture and lack of hepatosplenomegaly, we considered that the leukemia was still in the chronic phase. Because of normal blood level of the antidiuretic hormone (ADH) concentration and sufficient urine volume, the syndrome of inappropriate ADH secretion (SIADH) was unlikely, and sodium-losing nephropathy was suspected. After discontinuation of hydroxyurea, the urinary sodium excretion decreased and the patient's consciousness became clear concomitantly with improvement in the serum Na level. This patient appears to be the first case of hyponatremia caused by hydroxyurea.

We treated a patient with recurrent ovarian cancer with cancerous peritonitis by weekly paclitaxel (w-TXL) therapy (65 mg/m2). Abdominocentesis was not performed to eliminate ascites, in order to maintain higher quality of life (QOL), and critical adverse reaction was not seen for 12 months. We measured the TXL concentration in blood plasma and ascites after TXL infusion by HPLC method. The TXL titer in plasma was 427 ng/ml after infusion, 23 ng/ml after 24 hours and under 10 ng/ml after 48 hours. The TXL titer in ascites was 41 ng/ml after infusion, 37 ng/ml after 6 hours, 18 ng/ml after 12 hours, 10 ng/ml after 24 hours and under 10 ng/ml after 48 hours. TXL transportation from blood to ascites was good. This result suggested that intravenous infusion of TXL was effective for cancerous peritonitis treatment.

A 77-year-old man diagnosed with advanced gastric cancer underwent total gastrectomy with combined splenectomy and resection of the pancreatic tails in 1996. He was treated with 400 mg/day of UFT for 2 years. Serum CEA level was found to be elevated on July 5, 2001. He complained of left chest pain in December 2001. A 4 cm-sized tumor was detected in the region extending from the subcutaneous region to the left chest wall containing the osteolytic change of the left sixth rib. He was diagnosed with a chest wall metastasis from gastric cancer. He underwent radiotherapy with thermotherapy and was also treated with chemotherapy. TS-1 was administered at 80-100 mg/body/day, twice daily for 3 weeks followed by a 2-week rest interval as 1 cycle. As a results, shrinkage of the tumor was confirmed on February 14, 2002. The tumor was confirmed to have disappeared on April 17, 2002, by chest CT. A complete response of the metastatic tumor was achieved. The patient maintained a complete response for more than 12 months, but died from the chest wall metastasis recurrence and weakness on August 13, 2003. The only observed adverse event, was grade 2 leukopenia.

We report a case of chronic myeloid leukemia (CML) with clonal Philadelphia negative hematopoiesis arising after treatment with imatinib. A 45-year-old man was diagnosed as having Ph-positive CML. Therapy with MCNU and hydroxyurea was carried out for 12 days, and was then replaced by imatinib. A major cytogenetic response was obtained after 13 months of therapy with imatinib, but at the same time a new Ph-negative clone with trisomy 8 appeared in the bone marrow. Blood cell counts were still within normal limits. This observation indicates that patients on imatinib should be followed with bone marrow morphologic finding and routine cytogenetic testing, even after induction of a good response.