Diagnosis and treatment of mediastinal teratoid tumors

Among anterior mediastinal tumors affecting male patients of around 20 years old, mediastinal malignant teratoid tumor must be considered as one of the possibilities. Malignant teratoid tumor can be classified as seminoma, non-seminoma or mixed, according to clinical behavior. In the non-seminoma group, AFP and/or HCG can be the specific markers in the diagnosis or assessment of the effect of treatment. Chemotherapy with CDDP must be the first choice of treatment in these types of tumor, just as chemotherapy is the first choice of therapy in the treatment of small cell lung cancer, and surgery must be the adjuvant treatment to chemotherapy. On the other hand, seminoma can be treated by surgery and radiation, which has been proven to yield a good prognosis. In cases of seminoma which produces HCG and/or AFP, chemotherapy with CDDP must be added to surgery and radiation as in non-seminomatous mediastinal teratoid tumors, because the production of such markers in seminoma is considered to be one of the poor prognostic factors in the treatment of seminomatous mediastinal teratoid tumors.     

Diffuse B-cell lymphoma of anterior mediastinum cured by short-term administration of CDDP-containing regimen

The following report is of a case of diffuse B-cell lymphoma of the anterior mediastinum that was originally treated by resection and radiation in a patient who had pleural and subcutaneous metastases four months after operation. A total dose of 120 mg of CDDP, 60 mg of BLM, and 15 mg of VBL was administered in five weeks. The metastases completely disappeared by this dose alone, and the patient is alive and well seven and a half years after the chemotherapy.     

Intra-arterial chemotherapy with cis-diamminedichloroplatinum (CDDP) for primary mediastinal seminoma

Primary mediastinal malignant germinoma is a rare disease, and only about 15 patients have been reported in Japan. We treated a patient with this disease by intra-arterial CDDP infusion and observed good effects. A 29 year-old male was admitted to our hospital due to SVC syndrome in 1980. A right mediastinal tumor was detected, and the resection of this tumor was performed. Histological examination showed seminoma. Though postoperative Co irradiation was performed, radiation pneumonitis developed in the right lung. Subsequently, the tumor metastasized to the right kidney and spinal cord. After removal of the right kidney followed by Co irradiation, the clinical course was good. In 1987, a mass (10 x 6 cm) was detected in the left mediastinum, suggesting recurrence. Four courses of CDDP infusion into the left bronchial artery and left internal thoracic artery (1 course: 45-70 mg) were performed, and good effects were obtained. No side effects were observed, and the clinical course has been good until now. This case is of interest in evaluating the multidisciplinary treatment for mediastinal seminoma.     

Experimental chemotherapy of human testicular carcinoma transplanted in nude mice

The testicular carcinoma serially transplanted in nude mice with BALB/c genetic background was used for experimental chemotherapy. A stable growth and a high production of alpha-fetoprotein (AFP) were observed in this tumor line. The effect and side effect of Cis-platinum (CDDP) and other anticancer agents on this tumor line in nude mice were studied by the chemotherapy with single administration of CDDP 2 mg/kg, 4 mg/kg, 6 mg/kg and 8 mg/kg, and the combination chemotherapy with CDDP, Vinblastine (VBL) 0.1 mg/kg, Bleomycin (BLM) 0.5 mg/kg and Cyclophosphamide (CTX) 2 mg/kg. The body weight of the tumor bearing nude mice, the tumor size (length X breadth) and serum AFP level were measured every week up to 10 weeks after inoculation of the tumor mass. Six weeks after administration of these anticancer agents, the tumor mass was removed out and examined histologicaly. The effects of CDDP and other anticancer agents were observed as inhibition of the tumor growth and regression of the tumor mass. In the groups treated by the combination chemotherapy with either CDDP + VBL + BLM or CDDP + VBL + CTX, the most remarkable inhibition and regression were observed. The AFP levels were remarkably decreased in contrast with those of the control group. The changes of serum AFP levels were reflected in the tumor growth. The serum AFP levels fell down to normal level, however, the tumor mass was clearly recognized. The tumor tissue was damaged histologicaly by the single administration of CDDP. The most remarkable change was shown in the group treated by the combination chemotherapy CDDP 4mg/kg + VBL + BLM. The tumor cells were arranged one or two layers like the epithelium. This histological findings suggested that the malignant tumor could be differentiated to benign tumor. The side effect of CDDP and other anticancer agents was observed as a loss of weight. All of mice treated by the single administration at a dose of CDDP 6 mg/kg and 8 mg/kg died of the side effect of CDDP.     

Successful chemotherapy in undescended testicular and extragonadal germ cell tumors: report of 2 cases

Two patients with advanced germ cell tumor who entered complete remission following intensive combination chemotherapy, radiation therapy and surgical intervention are reported. A 28-year-old businessman presented with abdominal pain and masses associated with an elevated HCG level for which he underwent exploratory laparotomy. Large retroperitoneal masses were found and microscopical examination of the masses were revealed seminoma. Three courses of combination chemotherapy consisting of CDDP, VLB and PEP were given to the patient followed by radiation therapy to the parailiac, paraaortic, mediastinal and supraclavicular lymph nodes with boost irradiation to the paraaortic lymph nodes where the large masses were located. The other patient was a 21-year-old student who developed sharp precordial chest pain which proved to be due to a large mediastinal mass accompanied by an elevated AFP level. He was treated with radiation therapy to the mediastinum, surgical resection and combination chemotherapy. However, he showed recurrence in the lungs associated with rising AFP levels, and was given a salvage chemotherapy consisting of 3 courses of CDDP, ADR, PEP and Etoposide. Both patients were successfully treated with combined modalities of treatment including intensive chemotherapy and have been off therapy without recurrence for over 12 and 4 months, respectively.     

Evaluation of multidisciplinary treatment involving chemotherapy with cis-diamminedichloroplatinum, bleomycin (peplomycin) and 5-fluorouracil for advanced esophageal carcinoma]

Twelve patients with unresectable squamous cell carcinoma of the esophagus were treated with a combination chemotherapy regimen consisting of cis-diamminedichloroplatinum (CDDP), bleomycin (BLM) or peplomycin (PEP), and 5-fluorouracil (5-FU). Ten of them received radiation therapy additionally. CDDP was administered once every 4 weeks at a dose of 50 mg/m2. Methylprednisolone of 250 mg was given intravenously 4 times at the same day with infusion of CDDP. BLM or PEP was administered intravenously at a dose of 20 mg/m2 every 2 weeks and 5-FU was administered at a dose of 330 mg/m2 on days 1-5, 15-19, and afterwards every 4 weeks. All patients received at least two courses of chemotherapy. All of them were evaluable. Complete and partial responses were obtained in one and eight cases, respectively. Responsive rate was 75.0%. The median duration of response was 17.0 weeks. The median duration of survival was 44.0 weeks in all patients, 46.1 weeks in responders and 17.9 weeks in non-responders. Nausea, vomiting, leucopenia, fever, nephrotoxicity and radiation esophagitis were observed as side effects but most of them were mild and well tolerated. In conclusion, this regimen was considered to be very useful as the chemotherapy for primary esophageal carcinoma.     

Successful chemotherapy for mediastinal seminoma--a case report

A case with large primary mediastinal seminoma responded very well to chemotherapy. A 13-year-old boy was evaluated for complaints of edematous face and neck. Chest radiography and computerized tomography revealed a large anterior superior mediastinal mass. Needle biopsy demonstrated seminoma. After two-drug combination chemotherapy with vincristine and prednisolone and three-drug combination with vincristine, prednisolone and cyclophosphamide, there was a considerable regression of the mediastinal mass. The lower neck and mediastinum were irradiated at a dose of 3,750 rad after cessation of chemotherapy. The patient has been asymptomatic without evidence of recurrence for a follow-up period of more than four years.     

A case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP

We report a case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP. A 52-year-old male was diagnosed with type 3 gastric cancer of angulus (poorly differentiated adenocarcinoma) with left neck, Virchow, mediastinal and abdominal lymph nodes metastases. The patient was treated with 5 courses of M-FLP (MTX + 5-FU + LV + CDDP), and the effect of this therapy was PR, but the tumor was chemoresistant to the sixth course of this therapy. After 7 courses of M-FLP, docetaxel (TXT) with low-dose FP (5-FU + CDDP) was administered to the patient as second-line chemotherapy. After 2 courses of TXT with low-dose FP, the gastric cancer and metastatic lymph nodes were remarkably reduced and the effect of this therapy was PR. The toxic events were anemia (grade 2) and leukopenia (grade 3), which were treated with G-CSF. CDDP and 5-FU based regimens are considered as the first-line chemotherapy for metastatic advanced gastric cancer in Japan; however, a second-line chemotherapy has not been established. As in this case, a TXT based regimen is effective and well tolerated therapy as a second-line chemotherapy for metastatic gastric cancer after prior exposure to CDDP and 5-FU.     

Combination chemotherapy with cis-dichlorodiammineplatinum (11) (CDDP) and bleomycin BLM in advanced esophageal carcinoma

Five patients with advanced carcinoma of the esophagus were treated with a combination chemotherapy employing CDDP and BLM. One cycle of chemotherapy consisted of CDDP, 50 mg/m2, on day 1 and BLM, 15 mg/patient on days, 1, 7 and 14. Two partial remission and 2 minor responses were obtained. Overall response rates, ths, were 80%. The most adverse effect was nausea. No significant elevation in the serum creatinine or BUN was recognized. Furthermore, the method of CDDP administration was studied on the serum level by 15 minutes' infusion and by 24 hours continuous infusion. The CDDP levels in the serum and tissue were determined by flameless atomic absorption spectrophotometry. The CDDP level in the serum by 15 minutes' infusion was higher than that by 24 hours continuous infusion. These results suggest that combination chemotherapy with CDDP and BLM may be a useful method for the treatment of advanced esophageal carcinoma.     

A case of nonresectable scirrhous type gastric cancer successfully treated by low-dose cisplatin (CDDP), 5-fluorouracil (5-FU) and pirarubicin (THP)

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. Recently, the usefulness of combined cancer agent chemotherapy based on the concept of biochemical modulation has been reported. For example sequential MTX and 5-FU therapy, low-dose CDDP plus 5-FU, and the like. In this paper, we report the usefulness of low-dose CDDP plus 5-FU therapy in combination with pirarubicin (THP) for inoperable scirrhous type gastric cancer. A 32-year-old man who was suffering from scirrhous type gastric cancer with pyloric stenosis was treated with this regimen. Eight weeks after the start of therapy, his gastric capacity and lumen diameter had clearly increased, and he was taking ordinary meals. Ascites had also completely disappeared. CR has now been continued about 7 months. This regimen is considered to be promising for scirrhous type gastric cancers with a poor prognosis.     

Bleomycin, vinca alkaloid and cis-diamminedichloroplatinum combination chemotherapy for advanced testicular tumors

Thirteen patients with advanced testicular tumors (seminoma 2, non-seminoma 11) were treated with combination chemotherapy involving BLM, vinca alkaloid and CDDP (BVP) as induction therapy and followed with CPM, VCR and CDDP as maintenance therapy. BVP and COP administration was repeated every 3 and 4 to 8 weeks for 1 year, if there were no serious side effects. The overall response rate (CR + PR) was 92% with a 69% CR rate. At a mean follow-up of 30 months (7-52 month range), 54% of the patients were alive with no evidence of disease. Bulky metastases, failure to respond to prior chemotherapy and teratomatous metastases were considered to be poor prognostic factors. The toxicity of BVP was similar to that reported for CDDP, except that allergic reaction occurred in 3 patients after several courses of treatment. Two of the 3 went into anaphylactic shock.     

Primary seminoma in the middle mediastinum: case report in a 69-year-old male

Primary mediastinal seminoma is an uncommon tumor usually located in the anterior mediastinum. The majority of cases occur in young males. We report here an extremely rare case of a 69-year-old male with primary seminoma in the middle mediastinum. The patient had no complaints, but an abnormal shadow was seen in a routine chest X-ray. We performed a tumorectomy in the middle mediastinum, a thymectomy and an orchidectomy and added postoperative chemotherapy. It seems that the tumor was not associated with the thymus, so we believe the tumor did not stem from the embryonic thymus. Our case demonstrated that mediastinal seminoma does not always occur in the anterior mediastinum of young males. Although this case is rare, seminoma should be included among the possible diagnoses of a middle mediastinal mass.      

A complete response of an advanced oesophageal carcinoma treated with hyperthermic chemotherapy: a case report

A 56-year-old Japanese man with an advanced squamous cell carcinoma in the middle oesophagus was treated with a combination of hyperthermia, intravenous infusion of cisplatin (CDDP) and oral administration of oily bleomycin(BLM)-polyacrylate paste. After performing six sessions of hyperthermia treatment conducted at 42–45°C for 30 min with 150 mg of CDDP and 180 mg of BLM, a subtotal oesophagectomy and lymph node dissection were performed. A histopathological study of the resected specimen showed no residual viable cancer cells either in the oesophagus or in the dissected lymph nodes. There were no side effects or perioperative complications and the patient is now healthy and leading a normal life 10 months after operation without undergoing any further treatment, at the time of writing. The effect of small amounts of CDDP and the oral application of oily BLM were thought to be strongly enhanced by hyperthermia in the treatment of oesophageal squamous carcinoma, and this regimen is therefore recommended as a safe and effective strategy, especially for preoperative treatment.     

A complete response of an advanced oesophageal carcinoma treated with hyperthermic chemotherapy: a case report.

A 56-year-old Japanese man with an advanced squamous cell carcinoma in the middle oesophagus was treated with a combination of hyperthermia, intravenous infusion of cisplatin (CDDP) and oral administration of oily bleomycin(BLM)-polyacrylate paste. After performing six sessions of hyperthermia treatment conducted at 42-45 degrees C for 30 min with 150 mg of CDDP and 180 mg of BLM, a subtotal oesophagectomy and lymph node dissection were performed. A histopathological study of the resected specimen showed no residual viable cancer cells either in the oesophagus or in the dissected lymph nodes. There were no side effects or perioperative complications and the patient is now healthy and leading a normal life 10 months after operation without undergoing any further treatment, at the time of writing. The effect of small amounts of CDDP and the oral application of oily BLM were thought to be strongly enhanced by hyperthermia in the treatment of oesophageal squamous carcinoma, and this regimen is therefore recommended as a safe and effective strategy, especially for preoperative treatment.     

Chemotherapy of invasive bladder cancer

This article is a review of the results of systemic chemotherapy for invasive bladder cancer. Transitional cell carcinoma of the urinary tract including the urinary bladder, renal pelvis and ureter has been moderately responsive to chemotherapy. Many chemotherapeutic agents have been studied singly or in combination. Until about 10 years ago, adriamycin (ADM) was the most studied agent for treatment of invasive bladder cancer. However, the results of single agents and combination with ADM have been disappointing; the overall response rate was approximately 20%. With the introduction of cisplatin (CDDP), the efficacy of chemotherapy for invasive bladder cancer has improved significantly. As single agents, CDDP has a response rate of 30 % in 320 cases, methotrexate (MTX), 29% in 236 cases, ADM, 17% in 248 cases, vinblastine (VBL), 16% in 38 cases, and mitomycin C, 13% in 42 cases. Presently the most important agents in the treatment of this disease are CDDP and MTX, and the next most useful agents are ADM and VBL. Recent data from limited trials in patients with advanced bladder cancer suggest that combination chemotherapy regimens with these agents induces a high percentage of complete remissions (CR), an overall response rate between 50% and 70%, and a median response duration of longer than 6 months. Most active combination regimens are M-VAC (CDDP + MTX + ADM + VBL), CMV (CDDP + MTX + VBL), CM (CDDP + MTX) and CISCA (CDDP + ADM + cyclophosphamide). These combination regimens with M-VAC, CMV, CM and CISCA show a response rate of 57%, 57%, 46% and 46%, respectively. However, these drugs have a substantial toxicity and their combination has still been regarded as too hazardous. The attainment of CR in 20% to 40% of cases given these combination regimens has led to adjuvant and neoadjuvant chemotherapy.     

Primary anterior mediastinal seminoma

A review of the Mayo Clinic experience with primary anterior mediastinal seminomas involved 17 patients who had pure anterior mediastinal seminomas and four who had mixed germ-cell tumors containing seminomas. At follow-up, of the 17 patients with pure anterior mediastinal seminoma, nine had no evidence of disease and eight had died of metastatic disease. Of the four patients with mixed germ-cell tumor containing seminoma, two were alive at follow-up and two had died of metastatic disease. In the group with pure anterior mediastinal seminoma, these factors seemed to have been associated with a greater potential for progression of disease: older than 35 years of age, presentation with fever, superior vena caval syndrome, supraclavicular or cervical adenopathy, and roentgenographic evidence of hilar disease.     

Salvage chemotherapy in refractory testicular cancer

A treatment strategy for patients with refractory testicular cancer who failed in the initial therapy has not been established. Patients with metastatic testicular cancer are treated with BEP (BLM, etoposide, CDDP) therapy, which is recognized as the standard first line chemotherapy regimen. About 80% of patients attain complete remission (CR) with BEP therapy and following salvage surgery. The patients who fail to achieve CR or have recurrences during the period of follow-up will be candidates for salvage chemotherapy. Salvage chemotherapies include VIP (ETP, ifosfamide, CDDP) therapy or high dose chemotherapy with peripheral blood stem cell auto-transplantation (PBSCT); however, the effectiveness of these therapies is limited. Those who fail in these salvage therapies are treated with irinotecan hydrochloride (CPT-11) in Japan. Clinical trials with paclitaxel and gemcitabine have recently been started in the United States and Europe. Further investigations are necessary to develop more useful regimens with these novel anticancer agents for refractory testicular cancer.     

Platinum-based chemotherapy of primary extragonadal germ cell tumours: the Hellenic Cooperative Oncology Group experience.

Extragonadal germ cell tumours (EGCT) are uncommon, most frequently arise in the mediastinum and retroperitoneum and have variable responses to platinum-based chemotherapy. A retrospective analysis was performed on 38 patients with EGCT treated with cisplatin-based (CDDP) or carboplatin-based (CBDCA) chemotherapy between 1984 and 1998. Twenty-four patients had nonseminomatous germ cell tumours (NSGCT) and 14 seminoma. Twenty-two tumours arose in the mediastinum (13 nonseminomas, 9 seminomas) and 16 in the retroperitoneum (11 NSGCT, 5 seminomas). Initial surgery included complete resection in 1 patient, biopsy in 27 patients and debulking surgery in 10 patients. Complete response rates with chemotherapy +/- surgery were as follows: mediastinum 14 of 21 (66.66%) patients (8 of 12-75% NSGCT, 6 of 9-66.66% seminomas) and retroperitoneum 14 of 16 (87.5%) patients (9 of 11-81.81% NSGCT, 5 of 5-100% seminomas). One patient who underwent complete resection of a mediastinal malignant teratoma combined, received PVB chemotherapy on an adjuvant basis and remains alive and disease-free. Three additional seminoma patients who achieved partial response after chemotherapy remain alive and disease-free following mediastinal radiotherapy. All 14 patients with extragonadal seminomas remain alive with no evidence of disease at a median follow-up of 49 months (range 7-164), giving an overall survival of 100%. Nine of 13 (69.23%) patients with mediastinal NSGCT are long-term disease-free at a median follow-up of 43.5 months (range 7-152). Nine of 11 (81.81%) patients with retroperitoneal NSGCT remain alive and disease-free at a median follow-up of 56 months (range 14-110). Complete surgical resection of residual mass was undertaken in 10 patients (3 seminomas, 7 nonseminomas). The histology revealed necrosis/fibrosis in 6 patients (3 seminomas, 3 NSGCT) and viable cancer in 4 patients. Patients who had viable malignant cells in the resected specimens received two more courses of VelP chemotherapy. None of our patients had relapsed at the time of this analysis. None of our 6 patients who underwent testicular biopsy (1 patient) or orchiectomy (5 patients) due to suspicious ultrasound of the testis were found to have testicular tumour or fibrotic scar. In conclusion, this retrospective analysis showed significant responses in patients with either mediastinal or retroperitoneal NSGCT treated with CDDP- or CBDCA-based chemotherapy +/- surgery. All patients with extragonadal seminomas remain alive with no evidence of disease, regardless of the site at presentation.     

Basic study on the chemosensitivity test by miniaturized improved nucleic acid precursor incorporation assay (MINI assay)]

Miniaturized improved nucleic acid precursor incorporation assay (MINI assay) has been developed by Kern D. H. and Tanigawa N. et al since 1985. We investigated in vitro effects of mitomycin C (MMC), cisplatin (CDDP) and bleomycin (BLM) against A 549 lung cancer cells and HeLa cells by MINI assay. Results: 3H-thymidine (3H-TdR) uptake in the positive control was 734.2 cpm +/- 10 cpm. The cut-off level for in vitro sensitivity was defined as more than 80% inhibition of 3H-TdR uptake in the drug treated cells compared to the positive controls. A 549 cells were sensitive to MMC (81.6%), CDDP (78.6%), but not to BLM (-57%). HeLa cells were sensitive to MMC (91%), CDDP (79.4%), but not to BLM (43%). MINI assay could be done with fewer cells than other methods and the results were obtained within 5 days. This method was considered to be useful for the chemosensitivity test with human tumors.     

Response rate and cell-cycle changes due to intra-arterial infusion chemotherapy with cisplatin and bleomycin for locally recurrent uterine cervical cancer.

Intra-arterial infusion with cisplatin (CDDP) and bleomycin (BLM) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone. Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM. Two to four courses of the infusion therapy were given to each patient, and the response rate, the tumor and serum drug concentrations, and the cell kinetics in tumor tissue were evaluated. The response rate (CR+PR) was 71.4% according to the WHO criteria. There was no difference, in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders. Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment, both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors. These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy.