Beneficial effect of cisplatin based combination chemotherapy on adenocarcinoma of the lung

Cisplatin (CDDP) based combination chemotherapy has improved the response rate of non-small cell lung cancer (NSCLC). However, the survival benefit of CDDP-based chemotherapy in patients with NSCLC is still controversial. In order to determine whether CDDP had a meaningful impact on the course of NSCLC, the survival of patients treated by combination chemotherapy containing CDDP (CDDP arm: PVB; CDDP + vindesine + bleomycin, VIP; vindesine + ifosfamide + CDDP) was compared with that treated by chemotherapy without CDDP (no CDDP arm: COMP; cyclophosphamide + vincristine + methotrexate + procarbazine, MVB; mitomycin C + vindesine + bleomycin), retrospectively. Survival in CDDP arm (median survival time [MST]; 10.2 months) was significantly longer than in the no-CDDP arm (MST; 6.9 months) (p less than 0.01). These results indicate that CDDP-based combination chemotherapy can not only improve response rate but also prolong survival of NSCLC.     

Successful treatment for advanced hepatocellular carcinoma by hepatic arterial infusion of CDDP powder as second-line chemotherapy

A 72-year-old man with type C liver cirrhosis had suffered from hepatocellular carcinoma (HCC) since April, 2001. HCC spread diffusely all over the right lobe of his liver, and the serum alpha-fetoprotein (AFP) value increased up to 42,696 ng/ml in June of 2004. He was implanted with a port-catheter system, and hepatic arterial infusion chemotherapy (HAIC) using low-dose of CDDP and 5-FU was started. However, it was not effective and after 4 months, the serum AFP level increased up to 755,030 ng/ml, ascites appeared, and gastro-esophageal varices also spread. No definite metastasis was detected, then we started to second-line chemotherapy. He was then given HAIC using CDDP powder for intraarterial use (CDDP 50 mg/m(2)/20 min, monthly). After 3 courses, the serum AFP level decreased to 9 10 ng/ml, and abdominal CT revealed that the main tumor had regressed and ascites had disappeared. After one more course, the serum AFP value decreased to 8 ng/ml and complete response was achieved on abdominal CT imaging. There was no major complication related to the chemotherapy. HAIC for advanced HCC using LFP has been reported to achieve favorable results, but no other regimens have been proved to the standard for HCC. HAIC using CDDP powder for advanced HCC may be beneficial as the second-line chemotherapy.     

A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin/carboplatin

A 73-year-old male underwent lobectomy with ND2a lymph node dissection and resection of the superior vena cava for right lung cancer in December 1998 at Akita University Hospital. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT4 (SVC) N2M0, Stage IIIB). He received 1 course of a combination of cisplatin (CDDP) and etoposide (ETP) as postoperative adjuvant therapy. In March 2001, he again underwent partial resection of the right lung (S8) due to recurrence. In December 2001, a new left lung metastatic tumor was found. The patient was transferred to our hospital, where he was given 1 course of vinorelbine (NVB) 25 mg/m2 (day 1, 8) and CDDP 80 mg/m2 (day 1). Subsequently, he received 2 courses of vinorelbine (NVB) 25 mg/m2 (day 1, 8) and carboplatin (CBDCA) 430 mg/body (day 1). After the chemotherapy, a complete response (CR) of metastatic lesions was achieved. Adverse reactions were grade 3 neutropenia, grade 2 alopecia and grade 1 nausea/vomiting. The combination of vinorelbine and platinum agent (CDDP/CBDCA) is a useful regimen in treating recurrent non-small-cell lung cancer.     

A case of curatively resected AFP producing gastric cancer with massive lymph node metastasis effectively treated by neoadjuvant-chemotherapy of S-1 and CDDP

A 65-year-old man who had AFP producing gastric cancer with massive lymph-node metastasis was admitted to our institution. Because of bulky lymph-node metastasis, the tumor was considered unresectable. He was treated with neoadjuvant chemotherapy of S-1 and cisplatin (CDDP).S-1 (80 mg/m2/day) was administered for 21 consecutive days followed by 14 days rest as one course,and CDDP (60 mg/m2) was infused over 2 hours on day 8. After 1 course, radiographic examination showed remarkable improvement in the tumor size of the stomach, and computed tomography showed markedly reduced paraaortic lymph node metastasis. However, surgery was performed after 3 weeks,because of the adverse effect of diarrhea grade 3 after one course of the chemotherapy. This is a rare case in which neoadjuvant chemotherapy of S-1 and CDDP may well be an effective treatment for unresectable AFP producing gastric cancer with bulky lymph-node metastasis.     

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.     

A case of locally advanced gastric cancer responding to preoperative S-1/CDDP combination chemotherapy

A 59-year-old man visited our department with the complaint of an abdominal mass. After detailed examination, he was diagnosed with cT3 (SE) N2M0, cStage III C gastric cancer and underwent a 3 course preoperative S-1/CDDP combination chemotherapy. After tumor down-staging was achieved after the 3 course combination chemotherapy, a surgery was scheduled. The patient underwent distal gastrectomy with D2 lymph node dissection. Histopathological diagnosis was M, type 1, 75 × 35 mm, papillary>moderately-differentiated tubular adenocarcinoma [pT2 (MP), ly3, v0, pN2, Stage IIB]. The patient is now treated with oral S-1 as postoperative adjuvant chemotherapy on an outpatient basis, and there are no signs of recurrence as of 1 year after the surgery. Preoperative chemotherapy appears to be a promising treatment option for gastric cancer with extensive lymph node metastasis.     

A case of refractory testicular cancer showing complete response to high-dose chemotherapy with autologous bone marrow transplantation

A patient with stage III testicular cancer was treated by 3 courses of BEP therapy and a partial response was obtained. Afterwards he underwent resection of pulmonary residual tumors and was treated by 2 courses of PE therapy immediately after operation. However, a new pulmonary tumor appeared after the first course of PE therapy was completed. He was treated by high-dose chemotherapy (etoposide 1200 mg/m2, cyclophosphamide 120 mg/kg, CDDP 60 mg/m2) with autologous bone marrow transplantation. Three weeks after high-dose chemotherapy his metastatic pulmonary tumor showed cavity formation which disappeared after 3 months. Fifteen months after the high-dose chemotherapy, no evidence of disease has been seen even without maintenance therapy.     

An early phase II trial combining cisplatin, carboplatin and vindesine in patients with inoperable non-small cell lung cancer

We conducted an early phase II trial of advanced non-small cell lung cancer (NSCLC) to evaluate the response efficacy of a combination of cisplatin (CDDP), carboplatin (CBDCA) and vindesine (VDS). The twenty-four patients in the study had had no previous treatment. CDDP (15 mg/m2), CBDCA (200 mg/m2) and VDS (3 mg/m2) were administered on Day 1, CDDP (15 mg/m2) was administered on Days 2-5, and VDS (3 mg/m2) was administered on Day 8. We observed 9 partial responses (PR), with a total response rate of 39%. The overall median survival was 72 weeks, and the 1-year survival rate was 57%. Major toxicities were hematologic; leukopenia of grades 3 and 4 occurred in 25% patients, and thrombocytopenia occurred in 21%. Therefore, the combination of CBDCA with CDDP and VDS chemotherapy was effective against inoperable NSCLC with tolerable toxicities and a favorable median survival time.     

Long survival and effective treatment of unresectable gastric cancer by TS-1 based chemotherapy with a sequential combination

We report a case of peritoneal cancer dissemination and cytological appearance of cancer cells with Type 4 gastric cancer. Treatment with unichemotherapy and combination chemotherapy with TS-1 proved successful. The patient was a 58-year-old female,who complained of abdominal pain. She was diagnosed as unresectable Type 4 gastric cancer, T 3 NxH 0 P 1 CY 1 M 0, Stage IV (cytology: Class V). Thirteen days after surgery, chemotherapy with TS-1 (80 mg/body/day, 4 weeks) at 2-week intervals in 1 course was performed. However, due to side effects with marrow restraint of grade 1, we changed to the following chemotherapy regimen: TS-1 (80 mg/body/day, 2 weeks) at 4-week intervals as 1 course (23 courses in total). After 16 courses, a partial response (PR) was noted. As additional therapy to recover tumor marker (CA19-9) after 21 courses, combination chemotherapy with TS-1 (80 mg/body/day, 2 weeks) and CDDP (25 mg/body/day, day 1, 8, 15 drip infusion) was performed as one course. This chemotherapy was then performed in 3 courses and tumor markers did not deteriorate, so we changed docetaxel (DOC) (50 mg/body/day(day 1)) to CDDP, and tumor markers returned to the normal value. No recurrence and no side effects appeared (hematological or non-hematological) during this combination chemotherapy.     

Successful treatment of pure endodermal sinus tumors in adult men

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.     

Combination chemotherapy of TS-1, docetaxel and CDDP produces a remarkable response in a patient with advanced esophageal cancer

We report a patient with advanced esophageal cancer who achieved a complete response to combination chemotherapy of TS-1, docetaxel and CDDP. A 74-year-old man was admitted to our hospital for advanced esophageal cancer with a complaint of dysphagia. He received chemotherapy, consisting of TS-1 100 mg/body, docetaxel 35 mg/m(2), and CDDP 10 mg/m(2), every 3 weeks. TS-1 was administered for 14 days followed by 7 days rest; docetaxel and CDDP were administered by intravenous infusion at day one and day 8 after beginning TS-1. After three cycles of chemotherapy, his dysphagia disappeared, and endoscopic examination of the primary esophageal tumor showed a complete response. Endoscopic examination with biopsy confirmed the disappearance of the esophageal cancer. No severe side effects were observed during this chemotherapy. Combination chemotherapy of TS-1, docetaxel, and CDDP can thus be effective for advanced esophageal cancer.     

A case of lung cancer showing marked reduction of pleural effusion by bevacizumab in combination with carboplatin and paclitaxel

A 63-year-old man was admitted to our hospital because of dyspnea. Chest computed tomographic(CT)scans showed right pleural effusion. He was diagnosed with adenocarcinoma of the lung(cTXN2M1a, stage IV). Although combination chemotherapy with 80 mg/m / 2 cisplatin(CDDP)and 60 mg/m2 docetaxel hydrate(DOC)was performed for 3 courses, the pleural effusion increased. As he had a progressive disease, his chemotherapy was changed to a new combination of AUC5 carboplatin(CBDCA), 200mg/m / 2 paclitaxel(PTX)and 15 mg/kg bevacizumab. After 2 courses, the pleural effusion dramatically decreased. During 6-month follow-up after the initial consultation, there has been no exacerbation.     

Successful combination chemotherapy for a case of small cell carcinoma of the rectum with multiple liver metastasis

A 69-year-old-man with small cell carcinoma of the rectum and multiple liver metastases was admitted in December 1996. Poorly differentiated adenocarcinoma was preoperatively diagnosed in a biopsy specimen from the rectum. Chemolipiodolization using 50 mg DXR and 6 ml lipiodol was performed for the multiple liver metastases. Ten days later, he underwent rectal amputation including lymph node dissection combined with the implantation of reservoir for hepatic arterial infusion chemotherapy. After operation 5-FU (500 mg, days 1-5) and CDDP (10 mg, days 1-5) were injected for 3 weeks through hepatic arterial route. The metastatic lesions in the liver represented a good response to the chemolipiodolization, though the metastatic tumor in the liver S4 region did not disappear on CT scan. The histological diagnosis of the resected rectum revealed small cell carcinoma so we attempted additional chemotherapy according to the regimen for treatment of small cell lung cancer. ETP + CDDP therapy was performed, in which ETP (100 mg, days 1-3) and CDDP (80 mg, day 1) were intraarterially infused. After three courses of this therapy, he achieved a complete response (CR) for the liver metastasis. Two courses of ETP + CDDP therapy were additionally performed in the outpatient department, and treatment is currently continued by oral administration of ETP (75 mg/day). He has been free of the disease for 16 months with few side effects. The combination therapy of chemolipiodolization and hepatic arterial infusion chemotherapy with ETP and CDDP may assure a good prognosis for multiple liver metastases of small cell rectal cancer.     

A case of AFP producing early gastric cancer successfully treated with small dose CDDP and 5-FU (PF) therapy]

A case of AFP producing early gastric cancer successfully treated with a small dose of CDDP and 5-FU therapy administered intermittedly is reported with a review of the literature. A 63-year-old male was admitted to our hospital because of liver metastasis with a high level of serum AFP (185.8 ng/ml) three months after gastrectomy. Systemic chemotherapy was performed twice with a regimen of CDDP 20 mg and 5-FU 750 mg/day in 5 days. After hepatic arterial infusion chemotherapy (HAIC) was performed once, the patient obtained partial response according to CT scan and was discharged. After he underwent HAIC once as an outpatient, liver metastasis completely disappeared 5 months after surgery. He was administered oral 5-FU, 150 mg and Krestin 3.0 g/day and underwent HAIC with CDDP 20 mg and 5-FU 750 mg/day every 2 weeks. After serum AFP level was returned to the normal range 7 months after surgery; HAIC was performed every 4 weeks and continued until one year after surgery. One year and 11 months after surgery, serum AFP remains within the normal limit and there is no evidence of recurrence.     

A case of gastric cancer with multiple liver metastases responding to combined hepatic arterial and aortic infusion chemotherapy with cisplatinum, 5-fluorouracil,and levofolinate calcium

A 64-year-old man who had type IIc-like advanced gastric cancer with multiple liver metastases was admitted to our hospital. He underwent combined hepatic arterial and aortic infusion chemotherapy with cisplatinum (CDDP), 5-fluorouracil (5-FU), and levofolinate calcium (l-LV). After 4 weeks (2 courses) of chemotherapy, a partial response was achieved for the hepatic metastasis. Therefore, distal gastrectomy, right hepatectomy combined with caudate lobectomy, partial resection of the hepatic right lobe, and microwave coagulation therapy of the residual tumor of the hepatic right lobe were performed. With this operation, all tumor cells were removed or killed. Histopathologically, almost all of the primary tumor was fibrous tissue, and only a few sections of moderately differentiated adenocarcinoma observed in the subserosal layer. In the periphery of the metastatic lesion, residual well to moderately differentiated adenocarcinomas were observed, and in the center, only necrotic tissue was seen. The postoperative course was uneventful. Now, one year and seven months after the operation, he is followed as an outpatient. Combined hepatic arterial and aortic infusion chemotherapy with CDDP, 5-FU, and l-LV is thought to be an effective regimen for advanced gastric cancer with multiple liver metastases.     

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.     

A case of unresectable gastric cancer complicated by serious pyloric stenosis in which S-1 administration after gastrojejunostomy proved effective

We report a patient with unresectable gastric cancer who was effectively treated with S-1 after gastrojejunostomy. A 64-year-old man was referred to our hospital for anorexia and epigastric palpable mass. Upper gastrointestinal endoscopy revealed an ulcerous tumor in the antrum of the stomach, and gastric roentgenography showed pyloric stenosis. CT showed simultaneous multiple liver metastases. We performed gastrojejunostomy to allow oral intake. He was treated with daily oral administration of 120-80 mg S-1 for two weeks followed by one week rest as one course. The treatment was repeated for 19 courses until remission was observed. Weekly paclitaxel therapy (80 mg/m(2)/week) was then chosen as second-line chemotherapy. Administration was continued for three weeks with one-week rest. The treatment course was repeated for 6 courses. Bi-weekly administration of CPT-11 (80 mg) and CDDP (30 mg) was chosen as third-line chemotherapy. He died of progressive disease 2 years and 2 months after surgery. During chemotherapy, he maintained a performance status of 0 to 1, and maintained quality of life. This case suggested that the gastrojejunostomy was a useful method for treating unresectable gastric cancer, allowing the possibility of oral intake, and the use of S-1.     

Advanced non-small cell lung cancer responded to both vinorelbine and carboplatin over long-term outpatient treatment

We treated a patient with lung adenocarcinoma who responded to chemotherapy with vinorelbine (VNR) plus carboplatin (CBDCA) on an outpatient basis. The patient was a 68-year-old man. He visited a local physician complaining of wet coughing, headache and general fatigne. The symptoms remained unchanged and the patient was admitted to our department for treatment in June 2000. A massive shadow in the right upper lobe and multiple cerebral metastases were found. Based on this, the diagnosis was lung adenocarcinoma (T3N2M1, clinical stage IV). Whole-brain irradiation and systemic chemotherapy were initiated from July 2000. The patient received 1 course of systemic chemotherapy with vindesine (VDS) plus cisplatin (CDDP) on an inpatient basis. This regimen was replaced with combination therapy of paclitaxel (TXL) plus CBDCA in the outpatient setting, along with VNR plus CBDCA due to side effects caused by TXL. The cerebral metastases almost disappeared due to whole-brain irradiation. Chest CT after 3 courses revealed a reduction in primary tumor size. The VNR plus CBDCA combination therapy was continued for a further 6 courses. As the result, neither the primary tumor nor the cerebral metastases enlarged. The combination therapy with VNR plus CBDCA seems to be a useful regimen that can maintain high QOL and be conducted for a long term on an outpatient basis.     

A resected case of advanced gastric cancer with multiple liver metastasis responding to preoperative TS-1/CDDP chemotherapy

Case: A 75-year-old man was admitted to our hospital with hematoemesis. Gastrofiber-scopy revealed that type 3 gastric cancer was widespread in the lesser curvature. Multiple liver metastases 5 cm in diameter were shown on CT. We thought that the case was unresectable, and TS-1/CDDP chemotherapy was performed. TS-1 (80 mg/body/day) was orally administered and CDDP at 20 mg/body/day by intravenous drip infusion a week for 3 weeks followed by a drug-free 2 week period as the first course. After the third course, the primary lesion and the liver metastasis showed a partial response in terms of size. No serious drug adverse reaction was observed. Since there was no longer any reduction of the tumor, gastrectomy and coagulation therapy for liver metastasis were performed, and he has been alive for 15 months without recurrence. Combined use of TS-1 and CDDP is effective as neoadjuvant chemotherapy for advanced gastric cancer.     

A case of AFP-producing gastric cancer resected after efficient S-1/CDDP combination chemotherapy

A 62-year-old male was diagnosed as AFP-producing gastric cancer with lymph node metastases and multiple liver metastases. He was treated with S-1 and CDDP combination chemotherapy. At the end of the first course, both primary and metastatic lesions were remarkably decreased in size, and the serum AFP level was also decreased. The chemotherapy was effective against the cancer and led to a partial response (PR) according to the RECIST guideline. Following the nine months of PR, the primary lesion which had once nearly disappeared, emerged again. Because distant lymph node metastases and liver metastases were considered to have disappeared, distal gastrectomy with D2 lymphadenectomy was performed. The patient received S-1 monotherapy for 6 months after the operation. At present the patient has achieved progression-free survival for 1 year and 3 months after the operation. Though AFP-producing gastric cancer is known for its poor prognosis, combination treatment such as operation or hepatic arterial infusion chemotherapy may improve the prognosis in patients with advanced AFP-producing gastric cancer when systemic chemotherapy is effective.