Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combined modality therapy is an effective adjuvant therapy for many patients with clinically resectable rectal cancer. The indications for adjuvant therapy for rectal cancer are based on the pattern of failure after surgery. Despite radical surgery, local-regional failure frequently occurs in patients with transmural or node-positive rectal cancers. The incidence of treatment failure in the pelvis is directly correlated with the extent of transmural penetration (microscopic vs gross) and the additional risk of lymph node metastases. In the post-operative setting its use is dictated by pathologic stage and the type of operation (i.e. conventional surgery or a local excision). The choice of which post-operative adjuvant regimen to recommend in the non-protocol setting remains controversial. If 5-FU alone is used, then it is best administered by continuous infusion. In the preoperative setting, the use of adjuvant therapy depends on the clinical stage and the need for sphincter preservation. Phase I/II trials examining the use of newer chemotherapeutic agents such as Tomudex, UFT/leucovorin, CPT-11, oxaliplatin, eniluracil and capecitabine with preoperative radiation therapy are in progress. This review examines both the selection criteria and results of adjuvant combined modality therapy for patients with clinically resectable rectal cancer.
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PMID:Present indications for adjuvant therapy in resectable rectal cancer. 1197 5

Gastrointestinal tumors are among the most common cancers in the world. Palliative chemotherapy is widely used to treat patients with advanced or metastatic disease. The mainstay of chemotherapy for colorectal cancer is 5-fluorouracil (5-FU) modulated by leucovorin (LV), alone or in combination with oxaliplatin or irinotecan (CPT-11). Gemcitabine is currently the standard of care in patients with pancreatic cancer. There is no standard in gastric cancer, although cisplatin, 5-FU, and the anthracyclines are the most common drugs used. Pemetrexed, a new-generation antifolate antimetabolite, has demonstrated a 15% to 17% response rate in metastatic colorectal cancer, similar to those of other single agents in previously untreated patients. In patients with advanced pancreatic cancer, pemetrexed achieved a 6% response rate and a 28% 1-year survival rate, which is comparable to single-agent gemcitabine. Preliminary results in gastric cancer are encouraging. The generally mild side effect profile of pemetrexed, especially with folate supplementation and dexamethasone premedication, and the synergy between pemetrexed and drugs frequently used in gastrointestinal cancers, such as irinotecan, oxaliplatin, and gemcitabine, suggest that further clinical studies are indicated to determine the role of pemetrexed in the treatment of colorectal, pancreatic, and gastric cancers.
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PMID:Pemetrexed in patients with gastrointestinal carcinoma. 1202 92

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.
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PMID:[A case of rectal cancer with multiple liver metastases that responded dramatically to pharmacokinetic modulating chemotherapy/CPT-11 therapy]. 1204 Jun 84

The treatment of advanced non-small cell lung cancer requires histologic proof of diagnosis, careful staging, and assessment of each patient's performance status and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1, appropriate management consists of combination chemotherapy with a platinum (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine, vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established by large phase II or phase III studies should be followed. Variations in the toxicity patterns, schedules of administration, and economic considerations should guide the selection of the specific regimen. For patients who maintain a good performance status after first-line chemotherapy, second-line treatment may be considered. Current evidence supports the use of docetaxel as second-line treatment if the patient has not previously received this drug. Gemcitabine and paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and CPT-11 appear to be inactive as second-line therapy for patients who have previously received platinum-based chemotherapy. For patients with a PS of 2, single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the two should be considered. Patients with poor performance status should be treated with supportive measures designed to relieve pain and acute complications because any tumor-directed therapy has limited benefit. Special situations exist in which curative therapy for metastatic disease is a possibility. Patients who present with solitary sites of metastatic disease, particularly after a long disease-free interval and in the CNS may undergo definitive surgery or radiotherapy with curative intent. Some have also reported favorable outcomes for patients with solitary adrenal or bone metastases as well. Surgical treatment or definitive radiotherapy should not be employed unless a thorough restaging evaluation is performed that includes computed tomography scan of the chest and abdomen through adrenals, brain magnetic resonance imaging, and positron emission tomography scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the hypoxic environment of tumors, and the cell cycle are currently in development.
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PMID:Advanced non-small cell lung cancer. 1205 40

Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease. Irinotecan (CPT-11, Camptosar)-based regimens have improved survival in patients with metastatic disease and are being actively investigated in combination with pelvic radiation therapy for patients with rectal cancer.
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PMID:Combined-modality therapy for rectal cancer using irinotecan. 1210 5

Today, no effective chemotherapy regimen has been established for non-resectable or postoperative recurrent gastric cancer, and most such therapy seems to be palliative. Thus, a highly effective chemotherapy that allows good patient QOL is desired. We report three gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, CPT-11. The treatment protocol was tegafur 1,200 mg/body, days 1-12 (continuing 16 h, intravenously with 800 mg/body from 16 to 24 h, 400 mg/body from 24-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, 8-12, (16 h, one shot infusion), Isovorin 25 mg/body, days 1-5, 8-12 (16 h, one shot infusion), followed by CPT-11 100 mg/body, days 13 (one shot infusion). We performed 1 or 2 courses, and with 2 courses the CPT-11 dose was increased to 150 mg/body. The first patient was a 54-year-old female with advanced type 3 gastric cancer with liver metastasis (H3). After chemotherapy (2 courses), there was a 30% reduction in the advanced gastric cancer and a 95% reduction in the liver metastasis. The second patient was a 73-year-old male with recurrent type 1 gastric cancer in the remnant stomach 24 months after partial gastrectomy. After chemotherapy (1 course), there was a 45% reduction in advanced gastric recurrent cancer. The third patient was a 67-year-old male with advanced type 2 plus 3 gastric cancers with liver (H3) and abdominal lymph node metastases. After chemotherapy (1 course), there was a 70% reduction in the type 2 and 55% reduction in the type 3 advanced gastric cancer, and a 50% reduction in the liver metastasis and 35% reduction in the abdominal lymph node metastasis. The only adverse effect was grade 2 pancytopenia, gastrointestinal disorder, and alopecia. In conclusion, this regimen resulted in good intrachemotherapeutic QOL and was highly effective in advanced gastric cancer patients.
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PMID:[Three patients with advanced nonresectable and recurrent gastric cancer responding to chronomodulation chemotherapy with tegafur + cisplatin + isovorin followed by CPT-11 administration]. 1221 74

The anti-metastatic efficacy of MMI-166, which is a selective matrix metalloproteinase (MMP) inhibitor, in combination with CPT-11 was examined using two metastasis models of human gastrointestinal cancer cells. In the liver metastasis model, C-IH human colon cancer cells were injected into the spleen of athymic BALB/c nude mice. Daily oral (p.o.) dosing of MMI-166 at 200 mg/kg starting 1 day after tumor inoculation led to a significantly prolonged survival effect by inhibiting liver metastasis of C-1H tumor cells. CPT-11 (5 or 20 mg/kg) was administered intraperitoneally (i.p.) three times on day 3, day 7 and day 11 and also improved the survival of tumor-inoculated mice compared with the vehicle control. When MMI-166 was combined with CPT-11, the anti-metastatic efficacy was significantly augmented. Moreover, long tumor-free survival was noted in two of eight mice that were given the combination therapy but not either MMI-166 or CPT-11 monotherapy. In the peritoneal dissemination model, TMK-1 human gastric cancer cells were injected i.p. into nude mice. While both MMI-166, administered daily p.o. from day 1 at 200 mg/kg, and CPT-11, administered intravenously (i.v.) three times, inhibited the tumor dissemination and growth, the combination therapy of MMI-166 plus CPT-11 showed a greater inhibitory effect than each monotherapy. A hematotoxicity study demonstrated that CPT-11 alone significantly decreased the number of white blood cells (WBC) and bone marrow cells (BMC) in the mice during treatment, while the daily administration of MMI-166 alone had no such effect. More importantly, the combination therapy of MMI-166 with CPT-11 did not augment the hematotoxicity caused by CPT-11. An in vitro cytotoxicity study showed that MMI-166 itself neither has direct cytotoxicity in C-1H and TMK-1 tumor cells, nor does it augment the cytotoxicity of SN-38, an active form of CPT-11. The findings indicate that the augmented anti-metastatic efficacy in combination treatment was not simply due to the augmentation of direct cytotoxic activity, but was rather an additive or synergistic effect of anti-metastatic activities with different mechanisms. In conclusion, we demonstrated that the anti-metastatic efficacy against C-1H colon cancer and TMK-1 gastric cancer were augmented by the combination therapy of MMI-166, an orally active MMP inhibitor, with CPT-11. However, the hematotoxicity caused by CPT-11 was not augmented in the combination with MMI-166. Thus, the combination therapy of MMI-166 and CPT-11 exhibited potent anti-metastatic efficacy without increased hematotoxicity. These results point to the clinical advantage of using MMI-166 in combination with CPT-11.
Clin Exp Metastasis 2002
PMID:Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. 1240 89

Most colorectal cancers metastatic to the liver are resistant to chemotherapy and are not amenable to surgical resection. This study evaluated our 6-year experience (July 1992-July 1998) in treating patients with unresectable hepatic colorectal metastases refractory to systemic 5-fluorouracil (5-FU). One hundred fifty-three patients underwent cryosurgical ablation (CSA) of 5-FU-resistant hepatic metastases. The patients then received either hepatic arterial floxuridine (FUDR), systemic CPT-11, or no postoperative adjuvant chemotherapy. Number, size, and location of hepatic metastases, carcinoembryonic antigen (CEA) levels, and type of postoperative treatment were analyzed. One to 15 lesions were frozen (median number, 3; median size, 6 cm), for a total of 73 synchronous and 80 metachronous lesions. Overall median survival was 28.4 months from the date of diagnosis of liver metastases and 16.1 months from the time of CSA. After cryosurgery alone, median survival was 13 months, which was significantly shorter than the post-CSA survival of 23.6 months with adjuvant CPT-11 and 21.2 months with hepatic FUDR (P = 0.007). Predictors of survival included preoperative CEA, postoperative reduction in CEA, and adjuvant chemotherapy (P < 0.05). Neither size, number of lesions, nor tumor location impacted survival. At a median follow-up of 13 months, 67% of patients have recurred (35% hepatic, 16% extrahepatic, and 49% both). Twenty percent of the recurrences were in the lobe of the CSA site. The 25 patients who underwent a second CSA had a median survival of 28.4 months from CSA and 40 months from the date of diagnosis of liver metastases. These data indicate that CSA offers an effective alternative for unresectable patients resistant to 5-FU. Systemic CPT-11 or regional FUDR may further prolong survival after CSA.
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PMID:Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil. 1244 77

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.
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PMID:Multicenter phase II study of fractionated bimonthly oxaliplatin with leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer, pre-treated with chemotherapy. 1246 46

A 62-year-old male patient presented at the hospital because of left lower abdominal tumor. Based on preoperative examination and biopsy results, he was diagnosed with stage IV diffusely infiltrating colon cancer (scirrhous type) with paraaortic lymph node metastases. He underwent sigmoidectomy with D1 lymph node dissection and received systemic infusion of 5-FU 750 mg and l-LV 300 mg once a week. This chemotherapy produced no change in response in the paraaortic lymph node metastases for a long time. One year later, there were distant lymph node metastases including left inguinal and Virchow's lymph node, and systemic infusion of CPT-11 was performed. In addition, left inguinal lymph node was treated with irradiation therapy (total 50 Gy). The patient died of multiple organ failure 18 months after the operation. It is known that the prognosis in cases of diffusely infiltrating colorectal cancer is extremely poor. However, this case might suggest that intensive therapies with surgery and chemoradiation are useful in maintaining quality of life and improving survival.
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PMID:[A case of stage IV diffusely infiltrating colon cancer treated by surgical resection and chemoradiation therapy]. 1248 87


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