A successfully resected case of colorectal cancer with multiple liver metastases treated with systemic chemotherapy

The patient was a-54-year-old man. Sigmoidectomy was performed for sigmoid colon cancer in 1991. Partial liver resection in 1992 and microwave coagulation therapy (MCT) in 1994 were carried out for liver metastasis. Complete remission of the metastasis was achieved. In June 2002, multiple liver and lung metastases were identified. 5-FU, CDDP therapy was applied as systemic chemotherapy. The liver metastasis was improved and the level of CEA was reduced. However, a new lesion appeared in the right lobe of the liver, followed by an increase of the CEA level. Although CPT-11, 5-FU, CDDP therapy was applied, it was not effective. The reason was considered to be from the decrease of drug delivery resulting from an unbalanced blood supply in the right lobe of the liver. Right lobectomy and radio-frequency ablation was performed on June 17, 2003. The level of CEA was dramatically decreased. Additionally, CPT-11, 5-FU, CDDP therapy was applied. The patient has survived for 11 years after liver metastasis was first detected.     

A case of liver failure associated with liver damage due to mFOLFOX 6 after resection for multiple liver metastases from colorectal cancer

A case of colorectal cancer in a 60-year-old man became resectable after downstaging was achieved with mFOLFOX 6 for multiple liver metastases from colorectal cancer. The patient received 8 cycles of mFOLFOX 6 on the basis of a diagnosis of multiple liver metastases in the right and left lobes and a single metastasis in the right lung. After chemotherapy, the liver metastases showed partial response, and the lung metastasis stable disease. Because the lung metastasis was controlled and radical cure of the liver metastases was thought possible by resection, we performed right lobectomy of the liver. Postoperative progress was good, and we then planned a staged partial resection of the lung. However,on postoperative day 28, the patient was hospitalized again with liver dysfunction, which evolved into liver failure, in spite of conservative treatment. The patient died on postoperative day 95. The needle biopsy specimens of the liver taken on readmission showed bile duct occlusion, portal hypertension, and perisinusoidal fibrosis, and histopathology of the surgical non-tumoral liver specimen showed the same findings. We think that liver failure was triggered by resection of the liver which had been damaged by mFOLFOX 6. Recently, liver damage due to oxaliplatin was reported, and evaluation of liver injury is considered important before liver resection for colorectal liver metastases with neoadjuvant FOLFOX.     

A case of huge advanced rectal cancer resected successfully after chemotherapy with mFOLFOX6

The patient, a 75-year-old woman, who was referred to our hospital in April 2010 because of diarrhea and lower abdominal pain. Abdominal CT scan revealed a large tumor, over 8 cm in diameter within the pelvis, and colonoscopy detected rectal cancer. There was no obvious distant metastasis, although invasion to the uterus and regional lymph node metastasis was suspected. After admission, she had been suffering from tumor-accompanying symptoms such as fever, melena, and abdominal pain. Although loop sigmoid colostomy was performed, symptoms were unimproved, and the tumor had grown to 11 cm in diameter. Therefore, chemotherapy(mFOLFOX6)was started. After two courses of chemotherapy, the tumor-accompanying symptoms improved. Six courses of chemotherapy were administered, and subsequent examination revealed shrinkage of the tumor(effect judgment PR). Thirteen days after final chemotherapy, the tumor was successfully resected. Pathological diagnosis of the surgical specimen was tub2, pSI(sigmoid colon), pN0, and Stage II. The surgical margin was completely free of cancer(R0), and the histological effect of chemotherapy was judged as Grade 1b. The patient had received adjuvant chemotherapy with UFT+LV for half a year after discharge. She has been free from any sign of recurrence for 11 months. This case suggests that appropriate preoperative chemotherapy is useful for locally advanced rectal cancer.     

Recurrance of disappearing colorectal liver metastases after mFOLFOX6 regimen

Some colorectal liver metastases disappear during chemotherapy. Some of those disappearing lesions recur, but there are few reports aiming this topic. We examined 6 patients with 55 disappearing liver metastases (DLMs) during mFOLFOX6 regimen. Six DLMs were resected, of which 3 (50%) had remnant cancer cells. Among the 49 DLMs not resected, 9 recurred after 23.5 (4.2-41.4) months. Cumulative risks of recurrence were 10.5% at 1 year, 10.5% at 2 years and 27. 5% at 3 years. Among these, some went through additional mFOLFOX6 or FOLFIRI regimen after they disappeared, but there was no significant difference among the number of the chemotherapy regimen and whether recurrences occur or not. The recurrence rate of the DLMs may be small, but further review with larger-scale group of DLMs is warranted.     

A case of multiple liver metastases from colon cancer successfully treated with pharmacokinetic modulating chemotherapy

The present patient was a 54-year-old woman with anemia. After examination to identify the cause of anemia, she was diagnosed with sigmoid colon cancer and multiple liver metastasis. Sigmoid colectomy and insertion of an intra-hepatic arterial catheter were carried out. Histopathological examination of the resection specimen revealed well-differentiated adenocarcinoma, with a depth of tumor invasion of ss and positive lymph node metastasis. Pharmacokinetic modulating chemotherapy (PMC) was performed after the operation. The PMC consisted of oral UFT 300 to 400 mg/day every day and continuous arterial infusion of 5-FU 750 to 1,000 mg/24 h once a week. On a CT scan of the abdomen performed 6 months after the operation, the liver metastasis had disappeared and the patient was in complete remission (CR). PMC was continued, but the hepatic artery became occluded 1 year and 11 months after the operation, and so PMC was replaced by systemic chemotherapy of 5-FU plus levofolinate at 2 years after the operation. This chemotherapy was discontinued after 3 courses. At present, 2 years and 10 months after the operation, the patient remains in CR and is followed as an outpatient.     

A case of multiple liver metastases of colon cancer with PyNPase-positive successfully treated with 5'-DFUR

A 75-year-old man was diagnosed with transverse colon cancer. We therefore performed a transverse colectomy. Diagnosis of multiple liver metastases was made by intraoperative palpation, core needle biopsy and postoperative abdominal CT scan. 5'-deoxy-5-fluorouridine (5'-DFUR) 800 mg/day was administered orally after the surgery. After 2 months of administration, an abdominal CT scan showed the metastatic lesions of liver were reduced. After 8 months, an abdominal CT scan showed no evidence of liver metastases. Pyrimidine nucleoside phosphorylase (PyNPase), an enzyme that converts 5'-DFUR to 5-FU, has an important role in the expression of the anti-tumor activity of 5'-DFUR. Primary specimens of this case were regarded as PyNPase-positive. We think that administration of 5'-DFUR may be a useful treatment for advanced colon cancer that is PyNPase-positive.     

A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel

Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.     

A case of unresectable multiple hepatic metastases from colorectal cancer successfully treated with panitumumab therapy on third-line

In a patient with multiple liver metastases of colorectal cancer in whom tumor response had been achieved by 5-FU hepatic arterial infusion, the catheter for arterial infusion chemotherapy was occluded resulting in re-elevation of tumor marker levels. Second-line IRIS therapy using S-1 and CPT-11 was started. IRIS therapy reduced tumor marker levels to a degree greater than that previously achieved with 5-FU hepatic arterial infusion, and diagnostic imaging allowed a judgment of partial response. But tumor marker levels increased gradually. After all, diagnostic imaging allowed a judgment of progressive disease and an eminent elevation of tumor marker levels in one year. Third-line panitumumab therapy was started. Panitumumab therapy reduced tumor marker levels to a degree greater than that previously achieved with 5-FU hepatic arterial infusion and IRIS therapy, and diagnostic imaging allowed a judgment of partial response. We report herein a successful case. Hepatic arterial infusion therapy is one of the treatment methods characterized by a lower incidence of adverse reactions, relatively low cost, and expectation of high anti-tumor efficacy as compared to chemotherapy such as FOLFIRI. IRIS therapy does not require a port insertion and pump carrying, and its cost is about half of FOLFIRI therapy. When used as second-line therapy for unresectable colorectal cancer, non-inferiority of IRIS therapy to FOLFIRI therapy has been demonstrated in a phase II/III clinica (l FIRIS) study. We may say that IRIS therapy is promising as an equivalent to hepatic arterial infusion therapy in the treatment of liver metastases of colorectal cancer. In addition, we may say that panitumumab therapy is promising as an equivalent to hepatic arterial infusion therapy and IRIS therapy.     

Conversion chemotherapy using cetuximab plus FOLFIRI followed by bevacizumab plus mFOLFOX6 in patients with unresectable liver metastases from colorectal cancer

Recently, in patients with unresectable colorectal liver metastasis, liver resection sometimes becomes possible by intensive systemic chemotherapy, i.e. conversion therapy. However, among cases that do not respond well to first-line chemotherapy, it is rare that second-line chemotherapy results in a marked response allowing liver resection. We consider that the liver resection rate may be increased by initiating second-line treatment at an earlier stage before progression subsequent to first-line chemotherapy. We are conducting a multicentre Phase II study to evaluate the efficacy and safety of sequential chemotherapy using six cycles of cetuximab plus FOLFIRI (5-fluorouracil, folinic acid and irinotecan) followed by six cycles of bevacizumab plus FOLFOX (5-fluorouracil, folinic acid and oxaliplatin) as conversion chemotherapy. The primary endpoint is the liver resection rate during the bevacizumab + FOLFOX phase. Fifty patients are required for this study.     

A case of advanced breast cancer with multiple lung and liver metastases successfully treated with multi-disciplinary therapy

We report a case of advanced breast cancer with multiple lung and liver metastases (T4bN1M1) achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was a 63-year-old woman with slight jaundice who had ascites and an ulcerative breast lump with multiple lung and liver metastases. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although the ascites and the jaundice disappeared after chemotherapy, the response for breast tumor, metastatic sites in the lung and the liver were less satisfactory. Fifteen-months later, she received radiation therapy so that metastasis in the brain was recognized. But she had no neurological symptoms. Multi-disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.     

A case of advanced gastric cancer with multiple liver metastases successfully treated with TS-1 and CDDP

A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with TS-1 and CDDP: Akihiro Tsukahara, Kazuhiro Kaneko and Syuji Tanaka (Dept. of Surgery, Niigata Prefectural Koide Hospital) Summary A 70-year-old advanced gastric cancer patient with liver and lymph node metastases was treated by chemotherapy with TS-1 and CDDP. One course consisted of administration of TS-1 100 mg/body for 21 days followed by 14 days rest and infusion of CDDP 80 mg/body on day 8. At the end of 2 courses, the primary tumor showed a hypertrophic wall, but a partial response of the liver metastases (reduction ratio was 78.3%) and a complete response of the LN metastasis were achieved. PR and CR were maintained after 4 courses. There were no remarkable side effects for 4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced gastric cancer with liver and lymph node metastases.     

A case of rectal cancer with synchronous multiple liver metastases successfully treated with combined chemotherapy of modified FOLFOX6 and bevacizumab

We report here a case of rectal cancer with synchronous multiple liver metastases successfully treated with a combined chemotherapy of modified FOLFOX6 (mFOLFOX6) and bevacizumab. A 49-year-old man was admitted to our hospital due to constipation and anorexia. Abdominal ultrasonography and abdominal computed tomography (CT) scan revealed a rectal tumor (Rs) and abdominal abscess and 11 mm hepatic nodular lesion in S3 and 21 mm and 14 mm hepatic nodular lesions in S4. We diagnosed the patient had penetrated rectal cancer (Rs) and multiple liver metastases. We underwent a low anterior resection with D3 lymphadenectomy for the first time. After the operation, an 8 mm new liver metastasis in S6 appeared. We performed a combined therapy of mFOLFOX6 and bevacizumab 16 days after post operation. After the 8th course, there were a notable reduction in S3 and S4 liver metastases, and S6 liver metastasis was unidentifiable upon imaging. At this point, we underwent liver left lobectomy using the Liver Hanging Maneuver Method. After the second operation, there has been no recurrence and same chemotherapy is being continued.     

A case of multiple bone metastases from gastric cancer successfully treated with chemo-radiotherapy

A 75-year-old man underwent distal gastrectomy for gastric cancer (CY+, Stage IV) in June 2009. About 4 months after surgery, he had a strong pain in a right shoulder, and became writing difficulty. Some imaging examinations revealed multiple bone metastases, and it was diagnosed that the pain was caused by the tumor of cervical spine. Systemic chemotherapy was started using a regimen of S-1/CDDP, and radiotherapy (30 Gy) was performed for the cervical tumor at the same time. After two-course of the chemotherapy, the shoulder pain disappeared. About 12 months after surgery, he had a strong pain in a left leg, and became walking difficulty. Some imaging examinations revealed a progression of the tumor of lumbar spine. Radiotherapy (30 Gy) was demonstrated for the tumor. After the treatment, the leg pain disappeared. We experienced a case of multiple bone metastases successfully treated with chemo-radiotherapy.     

A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of paclitaxel]

A 57-year-old woman underwent modified radical mastectomy for left breast cancer (T4bN1M1: stage IV) in September 1999. Four-cycle CAF therapy had been administered as adjuvant therapy, but multiple recurrent tumors in the liver had grown bigger and the tumor marker (CEA) increased in value. Because CAF therapy was not effective, we tried to treat the patient with systemic and intra-arterial chemotherapy using paclitaxel. The side effects of this treatment were mild nausea and appetite loss, which required no treatments. This treatment reduced the multiple liver metastases on an abdominal CT and was thought to produce a partial response (PR). The time to response was the 101st day and PR has been continued.     

A case of colon cancer with multiple liver metastases and lymph nodes metastases successfully treated by 5'-deoxy-5-fluorouridine

In a 79-year-old man with ascending colon cancer, multiple liver metastases were detected by computer tomography. The patient underwent right hemicolectomy. Paraaortic lymph nodes metastases were found intraoperatively. After surgery, 5'-deoxy-5-fluorouridine (5'-DFUR) was administered orally at 600 mg daily. Abdominal CT showed disappearance of the liver metastases 6 months after operation. At a follow-up exam 24 months after the beginning of the chemotherapy, the patient remained in remission and reported no side effects. We consider oral administration of 5'-DFUR to be a useful treatment for advanced colon cancer.     

Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer

Background:

Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signalling with activity against all three VEGF receptors. Bevacizumab is an anti-VEGF-A monoclonal antibody with clinical benefit in previously treated metastatic colorectal cancer (mCRC).

Methods:

Patients with mCRC who had progressed following first-line therapy were randomised 1 : 1 : 1 to modified (m)FOLFOX6 plus cediranib (20 or 30 mg day⁻¹) or bevacizumab (10 mg kg⁻¹ every 2 weeks). The primary objective was to compare progression-free survival (PFS) between treatment arms.

Results:

A total of 210 patients were included in the intent-to-treat (ITT) analysis (cediranib 20 mg, n=71; cediranib 30 mg, n=73; bevacizumab, n=66). Median PFS in the cediranib 20 mg, cediranib 30 mg and bevacizumab groups was 5.8, 7.2 and 7.8 months, respectively. There were no statistically significant differences between treatment arms for PFS (cediranib 20 mg vs bevacizumab: HR=1.28 (95% CI, 0.85–1.95; P=0.29); cediranib 30 mg vs bevacizumab: HR=1.17 (95% CI, 0.77–1.76; P=0.79)) or overall survival (OS). Grade ⩾3 adverse events were more common with cediranib 30 mg (91.8%) vs cediranib 20 mg (81.4%) or bevacizumab (84.8%).

Conclusion:

There were no statistically significant differences between treatment arms for PFS or OS. When combined with mFOLFOX6, the 20 mg day⁻¹ dose of cediranib was better tolerated than the 30 mg day⁻¹ dose.     

Therapeutic effect of mFOLFOX6 for synchronous unresectable liver metastases from colorectal cancer

The current chemotherapy for metastatic colon cancer has improved an overall survival. In this study, we retrospectively analyzed the efficacy of mFOLFOX6 in colorectal cancer patients with synchronous unresectable liver metastases and compared the prognosis between before and after the administration of mFOLFOX6. The subject was 28 patients of colorectal cancer with synchronous unresectable liver metastasis who received mFOLFOX6 as a first-line treatment from 2005 to 2010. The median frequency of mFOLFOX6 was 10 times( range, 2-24 times), relative dose intensity of oxaliplatin was 75.0% (range, 42 .9-100), response rate was 32%, and median progression-free survival was 9 . 9 months. Surgical resection of colorectal liver metastases was performed to 4 patients (14.3%) as a conversion therapy. The overall survival of the patients with mFOLFOX6 was significantly better than that of 31 patients who received the chemotherapy via hepatic artery or the chemotherapy before the administration of oxaliplatin (31.8 months vs. 15 .1 months, p<0.01). Our results suggested that mFOLFOX6 treatment for unresectable liver metastases of colorectal cancer was made not only the conversion therapy possible, but it has improved the prognosis when compared with previous treatment without oxaliplatin.     

A case of multiple liver metastases from colon cancer successfully treated with modified pharmacokinetic modulating chemotherapy using Leucovorin

A 51-year-old man underwent right hemicolectomy due to ascending colon cancer with multiple liver metastases. Administration of modified pharmacokinetic modulating chemotherapy (PMC) using Leucovorin (intravenous infusion of 5-FU, 600 mg/m2/24 hours; oral administration of UFT, Taiho Pharmaceutical Co., Tokyo, Japan, 400 mg/day; and Isovorin, Wyeth Lederle Co., Tokyo Japan, 250 mg/body) was started postoperatively. Two months of modified PMC produced a drastic tumor reduction without any adverse reactions such as diarrhea or myelosuppression observed. At present the patient continues to tolerate the chemotherapy and is being followed as an outpatient clinic. This case suggests the usefulness of modified PMC using Leucovorin for progressive recurrent colon cancer.     

A case of multiple liver metastases from sigmoid carcinoma treated successfully with arterial infusion chemotherapy

A 63-year-old female, who had undergone sigmoidectomy for sigmoid carcinoma one year before, was admitted for multiple liver metastases. A urokinase-immobilized catheter was introduced into the proper hepatic artery via the gastroepiploic artery operatively. A daily arterial infusion of 5-FU (250 mg) was combined with a weekly arterial infusion of adriamycin (30 mg) or MMC (10 mg). After discharge, 5-FU (200 mg/day) was given orally and MMC (10 mg) was infused intraarterially every other week at an outpatient clinic. ADR or MMC was infused with angiotensin II, known to increase arterial blood supply to a malignant lesion. Ultrasonography demonstrated 35 to 50% reduction in tumor diameter. The density of metastases seen in computerized tomography became low indicating tumor necrosis. Plasma CEA level, which had initially been as high as 864 ng/ml, decreased rapidly and has remained within normal limits up to the present time. Arterial infusion chemotherapy using 5-FU, ADR or MMC in combination with angiotensin II seems to be effective in the treatment of multiple hepatic metastases from colorectal carcinoma.     

A case of liver metastases from gastric cancer successfully treated with induced hypertensive chemotherapy

We report a 77-year-old patient with gastric cancer who has survived 5 years after multidisciplinary treatment for both liver and brain recurrences. He underwent a D2 distal gastrectomy for macroscopically type 2 cancer at the lower third of the stomach on May 1997. The histopathological findings were as follows: O-IIc (SM2), poorly differentiated adenocarcinoma, pN2, ly2, v2, stage II. One year after surgery, a follow-up abdominal CT scan revealed multiple liver metastases. He received both hepatectomy and prophylactic hepatic arterial infusion of mitomycin C with induced hypertensive chemotherapy (IHC), a drug delivery system using the difference in blood flow between normal and tumor vessels by intravenously injected angiotensin-II. IHC was carried out monthly and the total dose of MMC was 74 mg (6 courses). Although he was disease-free for about 2 years, brain metastases were found on December 2000. He then underwent excision of the brain metastases and consecutive radiation by X-knife. Although he had a relapse of liver metastases on April 2002, he is still alive now. We consider multidisciplinary treatment including complete surgical resection as effective, even for recurrent or highly malignant gastric cancer.