A case of rectal cancer with multiple liver metastases that responded dramatically to pharmacokinetic modulating chemotherapy/CPT-11 therapy

A 67-year-old male patient suffering from rectal cancer complicated by multiple hepatic metastases underwent low anterior resection, cholecystectomy and hepatic arterial cannulation. He was treated postoperatively with arterial infusion pharmacokinetic modulating chemotherapy (PMC) and venous infusion CPT-11 (modified PMC). After three courses of modified PMC, a complete response (CR) of the hepatic metastatic lesions was noted. PMC/CPT-11 therapy was managed at our outpatient clinic, and seems to be a useful treatment option.     

A case of metastatic colon cancer to paraaortic lymph nodes and liver treated successfully with oxaliplatin combination chemotherapy

A 62-year-old female had been operated for sigmoid colon cancer and liver metastasis. We showed our original guideline of adjuvant chemotherapy for colorectal cancer to the patient. She selected UFT/LV 3 months after operation. Six months after operation,follow-up CT showed a paraaortic lymph node growing to 1.8 cm. We used FOLFIRI regimen for 3 series, but the nodule size did not change. Twelve months after operation, a new metastatic lesion measuring 2.0 cm appeared in the liver and the paraaortic nodule grew to 3.0 cm in size. We used FOLFOX 4 regimen, which had decreased the size of liver metastasis after only 2 series. After 6 series, liver metastasis disappeared completely and the paraaortic nodule was reduced to 1.2 cm. Making a detailed guideline of adjuvant chemotherapy at each hospital is helpful not only for doctors to have more clinical discretion but for patients to have better-informed consent.     

A case of recurrent gastric cancer that responded dramatically to docetaxel and 5'-DFUR combination chemotherapy

A 54-year-old man suffering from Borrmann type 4 advanced gastric cancer with pancreatic invasion and paraaortic lymph node metastases underwent a total gastrectomy, which was a radical C operation. From postoperative month 4, he visited our hospital with multiple liver metastases and increased lymph node metastases. After chemotherapy with CDDP and 5-FU, CDDP and UFT was administered on an outpatient basis. The effect of this therapy was PD, therefore, docetaxel and 5'-DFUR combination chemotherapy was performed as second line therapy. After 2 courses of this therapy, the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. The patient has undergone 4 courses of this therapy and is maintaining a clinical PR. It is conceivable that docetaxel and 5'-DFUR combination chemotherapy is useful for patients with advanced and recurrent gastric cancer, even if they had been treated with 5-FU administration as first line therapy.     

A case of unresectable gastric cancer successfully treated with combination chemotherapy of S-1 + CPT-11

A 70-year-old female, with type III gastric cancer underwent a staging laparoscopy in September 2004. Judging from the results of endoscopy, enhanced CT and staging laparoscopy, we finally diagnosed the patient with stage IV (T3N2MOHOP1CY1), and we started a combination chemotherapy of S-1 + CPT-11 (S-1: 80 mg/m2, day 1-21/35 days, CPT-11: 80 mg/m2, day 1, 15/35 days) from October 2005 to January 2007. Enhanced CT after 2 courses of the combination chemotherapy showed partial response (PR) in the primary lesion. PR continued up to the 13 courses. The CT and gastro fiberscope finally showed complete response (CR) with Group I in biopsy. During these procedures, the grade 3 of neutropenia, grade 1 of diarrhea and grade 1 of fatigue occurred as adverse events. In January 2007, Virchow and, abdominal lymph node metastases were detected, and that we judged the metastases as progressive disease (PD). Nevertheless, the second-line of paclitaxel chemotherapy (70 mg/m2, days 1, 8,15/28 days) has started and she was being judged PD after 2 courses, she died in April 2007.     

A case of advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy using CPT-11 plus S-1

Adjuvant chemotherapy for advanced gastric cancer has not yet been established. We report a patient with advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy consisting of CPT-11 and S-1. The patient was a 69-year-old woman diagnosed with large type 3 advanced gastric cancer with esophageal invasion and having No.3 lymph node metastasis (cT3, cN1, cM0, cStage IIIA), treated with 2 courses of CPT-11 plus S-1 as neo-adjuvant chemotherapy. Computed tomography after neo-adjuvant chemotherapy showed improvement of gastric wall thickness and reduction of lymph node metastasis. Subsequently, she underwent an operation. There was no lymph node swelling,so we performed curative surgery consisting of total gastrectomy, splenectomy, cholecystectomy, and D 2 lymph node dissection. Histological diagnosis was pT2 (MP), pN1, pStage II, and estimation of the histological change by chemotherapy was Grade 2. The course after surgery was good, and she was treated by S-1 after discharge. To date, 8 months after surgery, there is no evidence of recurrence. Combination chemotherapy consisting of CPT-11 plus S-1 can be performed safely as a neo-adjuvant treatment, and may be an effective treatment modality for advanced gastric cancer.     

An elderly patient with recurrent rectal cancer successfully responded to S-1 combined with CPT-11

An 80-year-old female visited our hospital with a chief complaint of anal pain and bleeding. The patient was diagnosed by colonoscopy to have rectal cancer which invaded the perineal region. A pelvic CT also revealed metastases to the lymph node located in the femoral artery. Miles operation was performed and a curative resection was successfully achieved. The pathological findings were poorly differentiated adenocarcinoma with pMP and pN2. Adjuvant chemotherapy was refused by the patient. Paraaortic lymph node metastasis was diagnosed by abdominal CT 6 months after the surgery. The patient was treated with S-1 combined with CPT-11. The S-1 (80 mg/m2) was orally administered for 2 weeks followed by a 2-week interval and CPT-11 (100 mg/m2) was also simultaneously administered biweekly. One cycle of chemotherapy was 28 days. The patient experienced grade 2 leukocytopenia, neutropenia, diarrhea and grade 1 alopecia. Abdominal CT revealed a partial response after 2 cycles. After 10 cycles, the patient continued to demonstrate a partial response. The S-1 combined with CPT-11 regimen for elderly patients was thus found to be very feasible and convenient, and we obtained a good compliance. As a result, this regimen was thus found to be promising for unresectable or recurrent colorectal cancer in elder patients. In the future, the efficacy and safety of this regimen should be verified in phase II clinical trial for elderly patients.     

A case of multidrug-resistant squamous cell lung carcinoma responding to S-1 plus CPT-11 combination chemotherapy

The patient was a 63-year-old man who consulted our hospital with complaints of a cough and breathing difficulties. His chest CT revealed a 25-mm mass in his right S1 hilar area with spiculation, disseminated nodule in right lung, and pericardial effusions. Also, bronchoscope and TBLB revealed squamous cell carcinoma. This patient was diagnosed as lung cancer (cT4N3M1, stage IV), and chemotherapy was initiated. The chemotherapy was given in the order of CBDCA (AUC3) +GEM (1,000 mg/m(2)), DOC (60 mg/m(2)), and VNR (25 mg/m(2)), and the tumor response was PD. S- 1 (120 mg/body/day, continuous administration for 2 weeks followed by 1 week of rest) was chosen as fourth-line treatment, and a breast CT detected tumor size reduction following completion of the first course. However, after completion of three courses, the breast CT found tumor-enlargement again. Then the chemotherapy was changed to amrubicin (35 mg/m(2)), but the treatment was discontinued due to skin rash. We once experienced a size reduction with S-1, so S-1 (100 mg/body/day, day 1-14) plus CPT-11 (60 mg/m(2), day 1, 7, 14) combination chemotherapy was conducted at 4-week intervals. After two courses were completed, tumor size reduction was observed by breast XP and CT. The response rate was 40.0%. Currently, seven courses were completed, and we will continue this treatment due to the tumor response of SD. The S-1 single treatment and S-1+CPT-11 combination chemotherapy showed efficacy for this difficult case of NSCLC with refractoriness to multiple cancer drug chemotherapy. This combination treatment should be investigated further for its therapeutic benefit.     

Neoadjuvant chemotherapy with combination of S-1 and CPT-11 in advanced rectal cancer - a case report

We report a case of advanced rectal cancer successfully treated with a combination of S-1 and CPT-11 as neoadjuvant chemotherapy. The patient, a 61-year-old man, had a rectal cancer with pelvic viscera invasion and severe stenosis. After colostomy for removing stenosis, he was treated with a combination of S-1 and CPT-11 (S-1 120 mg/body day on day 1-14, CPT-11 120 mg/body/day on day 1 and day 15, every 4 weeks). Seven courses of treatment resulted in a marked reduction of the primary tumor and disappearance of invasion. Subsequently, rectal amputation for curative intent was done. No surgical complication was observed. On microscopic examination, only a few tumor cells were detected in the granulation tissue of the resected rectum and no tumor cells in dissected LNs. This case demonstrates the effectiveness and safety in a neoadjuvant setting of a combination of S-1 and irinotecan for rectal cancer.     

A case of drug-induced interstitial pneumonia caused by S-1 and CPT-11 combination therapy for advanced colon cancer

The patient was a 77-year-old woman admitted for nausea and abdominal pain. Computed tomography (CT) revealed advanced ascending colon cancer with liver metastasis. After operation, we started combination chemotherapy of S-1 and irinotecan (CPT-11); S-1(80 mg/m2) administered orally for consecutive days followed by 14 days rest.CPT -11 (100 mg/m2) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent dyspnea with severe hypoxemia after the first course of combination chemotherapy of S-1 and CPT-11.CT scan showed diffuse interstitial lesions with ground glass opacity on both lungs. Steroid pulse therapy with oxygen therapy remarkably improved her symptoms, and abnormal findings on CT scan also resolved. Drug lymphocyte stimulation test was positive against S-1 and negative against CPT-11. These findings were consistent with S-1-induced lung injury. Drug -induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1 and CPT-11 combination therapy present high fever and dyspnea.     

A long survival case of advanced colon cancer with lung metastasis and cancerous pleuritis responding to CPT-11 and S-1 combination therapy

A 71-year-old man underwent right hemicolectomy for an ascending colon cancer (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil was performed, but CT scans and FDG-PET, conducted in May 2003, revealed cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed. Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day; day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed a partial response. Only grade 2 vomiting was noted as an adverse reaction to the treatment, however, the patient has been managed on an outpatient basis for the last 3 years with good QOL and the cancer under control. This case suggests that this combination therapy can be expected to be highly effective as a safe approach for continuously maintaining the QOL of patients with advanced or recurrent colorectal cancer.     

A case of advanced gastric cancer with obstructive jaundice that responded to TS-1/CPT-11 combination therapy after percutaneous transhepatic cholangio drainage

TS-1/CPT-11 combination therapy was carried out in a case of advanced gastric cancer with liver and lymph node metastases and obstructive jaundice after percutaneous transhepatic cholangio drainage (PTCD). Regression of the primary carcinoma and reduction in size of metastases were observed. Grade 1 fatigue and grade 2 neutropenia were noted as adverse reactions to the treatment. TS-1/CPT-11 combination therapy was useful in this case of advanced gastric cancer with liver and lymph node metastases.     

A case of advanced gastric cancer with pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases responding to combination chemotherapy of S-1 and irinotecan(CPT-11)

A 70-year-old woman with pulmonary carcinomatous lymphangitis and paraaortic lymphnode metastases due to gastric cancer, was treated by combination chemotherapy of S-1 and irinotecan(CPT-11). After one course of the chemotherapy, pulmonary carcinomatous lymphangitis and paraaortic lymphnode metastases were remarkably improved. Diet intake was improving and cancer pain remarkably declined. Because the origin of gastric cancer was not improved, total gastrectomy, distal pancreatectomy and splenectomy were performed. After surgery, relapse of pulmonary carcinomatous lymphangitis caused death of the patient. The combination chemotherapy of S-1 and CPT-11 was effective for pulmonary carcinomatous lymphangitis and paraaortic lymphnodes metastases due to gastric cancer. However, careful consideration is required since surgery is performed on a patient who had suffered pulmonary carcinomatous lymphangitis.     

A case of metastatic colon cancer treated with oxaliplatin combination chemotherapy

A 77-year-old male had been operated for ascending colon cancer with liver metastases. After hepatic artery injection therapy and CPT-11 plus 5'-DFUR combination therapy, oxaliplatin-based systemic chemotherapy was performed. Consequently, the tumor size was controlled for about 10 months. During the chemotherapy, we observed grade 3 neurological toxicity, but not grade 3-4 blood toxicity. Thus, the QOL of the patient was properly maintained. We conclude that the oxaliplatin-based chemotherapy may be useful for patients suffering 5-FU and CPT-11 resistant metastatic colorectal cancer in Japan.     

A case of advanced ovarian carcinosarcoma that responded remarkably to neoadjuvant chemotherapy of combined CPT-11 and CDDP

Carcinosarcoma of the ovary is a very rare and highly malignant neoplasm that accounts for less than 1% of ovarian neoplasms. Survival of patients with advanced stage cancer is poor and the best treatment is not clear. We report the case of a 60-year-old woman who had Stage IV advanced heterogeneous ovarian carcinosarcoma with lung and liver metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination CPT-11 (60 mg/m2, day 1, 15) and CDDP (60 mg/m2, day 1). Tumor markers of CA125 and LDH decreased remarkably to the normal level after 3 and 4 courses of chemotherapy, respectively. After 7 courses of chemotherapy, the ovarian tumor was obviously reduced, and the lung and liver metastases had disappeared. The patient was then able to undergo surgery. The current case suggests that combination CPT-11 and CDDP is effective against advanced ovarian carcinosarcoma.     

A case of non-curatively resected colon cancer with liver and lymph node metastases treated by TS-1/CPT-11 combination therapy

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.     

A case of rectal cancer with multiple liver and peritoneal metastases that responded dramatically to low-dose 5-FU plus LV and CDDP combination chemotherapy

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.     

A case of recurrent colon cancer with urinary bladder, para-aortic lymph nodes, and spleen metastases successfully treated with CPT-11

The patient was a 71-year-old woman with sigmoid colon cancer with urinary bladder invasion, for which sigmoidectomy with D 3 lymphadenectomy and partial cystectomy was performed. After surgery, the patient was started on 4 courses of 6-week systemic chemotherapy (500 mg/m(2) 5-FU and 200 mg/m(2) l-LV weekly). However, 4 months later, CT revealed local recurrence in the urinary bladder and recurrence in the para-aortic lymph nodes and spleen. Therefore, low-dose CPT-11 therapy (40 mg/m(2) once per week) was instituted, which achieved a complete response as revealed by CT for response evaluation 5 months after the start of therapy. Up to the present, after 8 months no recrudescence or recurrent lesions in other organs have been observed. The patient developed mild side effects such as grade 1 nausea, anorexia, and leukopenia, but has a well-maintained QOL.     

A case of metastatic liver tumor of colorectal cancer responding to low-dose CPT-11 chemotherapy

We report a case in which low-dose CPT-11 chemotherapy was effective for metastatic liver tumor of sigmoid colon cancer. A 49-year-old male with metastatic liver tumor, who had undergone sigmoidectomy with D2 lymphadenectomy, was treated by low-dose CPT-11 chemotherapy (CPT-11 30 mg/m2 x 3 days, every 2 weeks). After 7 courses of this chemotherapy, CT and ultrasound examinations showed a reduction of tumor size in the liver. This chemotherapy also showed no high grade toxicities. Therefore, low-dose CPT-11 chemotherapy seems to be effective for metastatic colorectal cancer, and safe in view of toxicities.     

Highly advanced gastric cancer that responded to neoadjuvant combination chemotherapy with docetaxel/CDDP/S-1 (DCS)

A 60-year-old male was found to have advanced gastric cancer and multiple lymph node metastases. Since curative surgery was concluded to be unfeasible, we tried neoadjuvant chemotherapy with the aim of controlling the lymph node metastasis. S-1 (80 mg/m2) was administered orally for two weeks then followed by 2-week rest period. CDDP (60 mg/ m2) and docetaxel (40 mg/m2) were simultaneously administered on day 1. Two courses of treatment resulted in marked shrinkage of the primary lesion and a reduction in size of the lymph nodes. The results were evaluated as a clinical PR based on RECIST, and radical resection was considered possible. The patient experienced a grade 3 leukocytopenia and neutropenia as adverse events of the chemotherapy. Total gastrectomy, splenectomy, and D2 lymph node dissection were performed with curative intent, and the postoperative course was uneventful. Histological examination of the surgical specimens revealed almost complete disappearance of cancer cells in the primary lesion in the stomach and complete disappearance in the lymph nodes. Pathological efficacy was Grade 2. The patient experienced a grade 3 appetite loss, and the adjuvant chemotherapy (S-1 regimen) was discontinued. The patient died of peritoneal dissemination eight months after the operation. We concluded that DCS as neoadjuvant chemotherapy was a promising strategy for patients with highly advanced gastric cancer because of its rapid antitumor effect.     

Recurrent gallbladder carcinoma treated with combination chemotherapy with gemcitabine, CPT-11 and S-1--a successful case with metastatic tumors replaced by marked calcification

We described a case with recurrent gallbladder carcinoma, successfully treated by combination chemotherapy using gemcitabine, CPT-11, and S-1 that was administered as second-line chemotherapy after failure of gemcitabine monotherapy. The level of CA19-9 was normalized three months later, and metastatic tumors of the liver were calcified. She had received the combination chemotherapy for 15 months and is now alive.