A clinical-study of immunotherapy versus endocrine therapy versus chemotherapy in the treatment of advanced pancreatic adenocarcinoma

The advanced carcinoma of pancreas still remains an untreatable disease. Both chemotherapy and hormono-therapy seem not to prolong the survival time. Also immunotherapy with IL-2 has been shown to have no efficacy. Our experimental studies suggested the possibility of enhancing the antitumor activity of IL-2 by the administration of immunomodulating neurohormones, such as melatonin (MLT). This study was carried out to evaluate the efficacy of IL-2 plus MLT in advanced cancer of the pancreas. Fifty patients, with advanced adenocarcinoma of the pancreas, were randomized to receive chemotherapy consisting of 5-FU plus folates, endocrine therapy with LHRH and somatostatin analogues, supportive care alone or immunotherapy with subcutaneous low-dose IL-2 plus MLT. A partial response was obtained in 1/13 patients treated with chemotherapy and in 2/12 patients receiving immunotherapy; no tumor regression was seen in the other groups. The percent of survival at 1 year achieved in patients treated with immunotherapy was significantly higher than in the other groups tested (3/12 vs 1/38; p<0.02). This preliminary study would suggest that the immunotherapy with IL-2 plus MLT may represent a new promising treatment of advanced pancreatic adenocarcinoma.     

Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract.

The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma.     

Efficacy and tolerability of cancer neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin - a progress report of 200 patients with advanced solid neoplasms

The recent advances in psychoneuroimmunology have demonstrated the existence of a psychoneuroendocrine control of the antitumor immunity. Our previous preliminary studies indicated the possibility of amplifying the biological and therapeutic efficacy of IL-2 cancer immunotherapy by immunomodulating neurohormones, mainly the pineal indole melatonin (MLT), in most advanced solid tumors, including those which generally do not respond to IL-2 alone. This study reports on the results obtained by low-dose IL-2 plus MLT in 200 patients with advanced solid neoplasms, for whom no other effective standard therapy was available. Non-small cell lung cancer, pancreatic adenocarcinoma, hepatocarcinoma, colon cancer and gastric cancer were the neoplasms most frequently detected in our patients. In addition, all patients had a life expectancy less than 6 months. IL-2 was given subcutaneously at 3 million IU/day for 6 days/week for 4 weeks; MLT was given orally at 40 mg/day. In non-progressing patients, a second cycle was given after a 21-day rest period; then, patients underwent a maintenance period consisting of one week of therapy every month until progression. A complete response (CR) was achieved in 4 patients (hepatocarcinoma 2; pancreas 1; gastric cancer 1), a partial reasponse (PR) was achieved in 36 patients (lung 12; liver 6; stomach 4; pancreas 3; colon 3; breast 2; miscellaneous 6). Tumor response rate (CR+PR) was 40/200 (20%) patients. Longer than one year survival was achieved in 79 (39%) patients. Toxicity was mild in all patients, and therapy was administered as a home therapy. The present study confirms in a great number of patients the possibility to induce objective tumor regressions in most advanced solid tumor histotypes by low-dose IL-2 plus MLT. Thus, immunotherapy with IL-2 and MLT may be considered as a new well tolerated and effective therapy of almost all advanced solid tumors, including those which do not respond to IL-2 alone or to chemotherapy.     

Preoperative neuroimmunotherapy with subcutaneons low-dose interleukin-2 and melatonin in patients with gastrointestinal tumors - its efficacy in preventing surgery-induced lymphocytopenia

Our previous studies have shown that a preoperative injection of high dose IL-2 is able to abrogate surgery-induced immunosuppression in colorectal cancer patients. Moreover, our previous clinical investigations have indicated the possibility of amplifying IL-2 activity by a concomitant administration of the pineal immunomodulating hormone melatonin (MLT). On this basis, a biological study was performed to investigate the immune effects of a preoperative biotherapy consisting of low-dose IL-2 plus MLT in patients with gastrointestinal tumors. The study included 20 consecutive patients with gastrointestinal tract tumors, who underwent radical or palliative surgery. Patients were randomized to receive no preoperative treatment or a presurgical neuroimmunotherapeutic regimen consisting of low dose of IL-2 and MLT. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days in combination with MLT at 40 mg/day in the evening. Patients underwent surgery within 36 h from the last IL-2 injection. The mean number of lymphocytes, T lymphocytes and NK cells significantly decreased during the postoperative period in control patients, whereas it increased in patients pre-treated by immunotherapy. CD25-positive mean cell number increased in both groups of patients; however, postoperative mean number of CD25 expressing cells was significantly higher in patients pretreated with IL-2 and MLT than in controls. No immunotherapy-related toxicity occurred. This preliminary study would suggest that a neuroimmunotherapeutic regimen with low-dose IL-2 and MLT given preoperatively is a well tolerated therapy, which is able to prevent surgery-induced lymphocytopenia in cancer patients. This perioperative manipulation of host anticancer defenses could have a prognostic role in the clinical course of the neoplastic disease.     

Neuroimmunotherapy of human cancer with interleukin-2 and the neurohormone melatonin: its efficacy in preventing hypotension

The pineal hormone melatonin (MLT) has been shown to influence many biological functions, including immune response, cancer growth and brain neurotransmitter contents. On the basis of its biological properties, a study was started to evaluate the influence of MLT on IL-2 immunotherapy toxicity. The study was carried out in metastatic renal cancer patients. Thirty-three 5-day courses of IL-2 at a daily dose of 3 x 10(6) Cetus U/m2 were randomized to consist of IL-2 alone or IL-2 plus MLT (10 mg/day orally at 8.00 p.m.). The frequency of episodes of severe hypotension was significantly greater during IL-2 alone than during IL-2 + MLT. Moreover, the depressive symptomatology occurred more frequently during IL-2 alone. No other toxicity, including capillary leak syndrome, vomiting and fever, were significantly influenced by the concomitant treatment with MLT. These preliminary results would suggest that the pineal hormone MLT may be successfully associated with IL-2 in the immunotherapy of human tumors.     

A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma.

Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 (IL-2) is not co-administration of another cytokine, but the association with immunomodulating neurohormones, in an attempt to reproduce the physiological links between psychoendocrine and immune systems, which play a fundamental role in the regulation of the immune responses. In particular, the association with the pineal neurohormone melatonin (MLT) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone. To confirm these preliminary results, a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma. The study included 80 consecutive patients, who were randomised to be treated with IL-2 alone subcutaneously (3 million IU day-1 at 8.00 p.m. 6 days a week for 4 weeks) or IL-2 plus MLT (40 mg day-1 orally at 8.00 p.m. every day starting 7 days before IL-2). A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone. A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone. Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone (11/41 vs 1/39, P < 0.001). The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group (19/41 vs 6/39, P < 0.05). Finally, the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone; on the contrary, the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone. The treatment was well tolerated in both groups of patients. This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy.     

Immunotherapy with low-dose interleukin-2 in association with melatonin as salvage therapy for metastatic soft tissue sarcomas

Polychemotherapy represents the only standard medical therapy of metastatic soft tissue sarcomas (STS), whereas the recent biotherapies with cytokines, such as interleukin-2 (IL-2), seem not to have a relevant therapeutic role. The pineal hormone melatonin (MLT), whose immunomodulating activity is well known, would seem to exert a direct cytostatic action on STS cell proliferation. Moreover, MLT has been proven to amplify IL-2 efficacy. On this basis, a pilot phase II study with low-dose IL-2 plus MLT has been performed in untreatable metastatic STS patients. The study included 13 evaluable metastatic STS patients with poor PS, who progressed on at least one previous polychemotherapeutic line. IL-2 was injected subcutaneously at 3 million IU/day for 6 days/week for 4 weeks and MLT was given orally at 40 mg/day in the evening. A partial response was achieved in one patient with leiomyosarcoma. Eight other patients had a stable disease (SD) whereas the remaining 4 patients progressed. A survival longer than 1 year was achieved in 6/13 patients and the percent of 1-year survival was significantly higher in patients with response or SD than in the progressed ones (6/9 vs 0/4). Mean increases in lymphocyte and eosinophil numbers were significantly higher in patients with response or SD than in the progressed ones. These preliminary results would suggest that immunotherapy with low-dose IL-2 plus MLT may have some impact at least on the survival time of untreatable metastatic STS patients with poor clinical conditions.     

Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer.

The metastatic non-small cell lung cancer (NSCLC) still remains an untreatable disease, and the role played by chemotherapy has yet to be defined. The new immunotherapeutic strategies, such as interferon and IL-2, seem to be also less effective, since they generally determine only a stabilisation of disease. On the basis of previous experimental results suggesting a synergistic action between IL-2 and the pineal neurohormone melatonin (MLT), a study was started to evaluate the clinical efficacy and toxicity of a neuroimmunotherapeutic combination consisting of IL-2 plus MLT as a first line therapy in metastatic NSCLC. The study included 20 patients (adenocarcinoma: 10; epidermoid cell carcinoma: 7; large cell carcinoma: 3). MLT was given orally at a dose of 10 mg day-1 at 8.00 pm every day, starting 7 days before the onset of IL-2 administration. IL-2 was given subcutaneously at a dose of 3 x 10(6) IU m-2 every 12 h for 5 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In responder patients or in those with stable disease, a second cycle was given after a rest-period of 21 days. A partial response was achieved in 4/20 (20%) patients. Ten other patients had a stable disease (50%), whereas the last six patients progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapeutic therapy with IL-2 and the pineal hormone MLT may represent a new effective and well tolerated treatment in metastatic NSCLC, with results comparable to those obtained with chemotherapy, but with an apparent lower biological toxicity.     

In vivo stimulation of IL-12 secretion by subcutaneous low-dose IL-2 in metastatic cancer patients.

Despite the well-demonstrated involvement of both interleukin 2 (IL-2) and interleukin 12 (IL-12) in the activation of host anti-cancer response, the knowledge of IL-2-IL-12 interactions has still to be better investigated. This study was performed to evaluate the effects of subcutaneous (s.c.) low-dose IL-2 on IL-12 secretion in metastatic cancer patients. The study included 19 evaluable metastatic renal cell cancer patients, who received s.c. low-dose IL-2 (6 MIU day(-1) for 6 days per week for 4 weeks) as a first-line immunotherapy of their metastatic disease. Serum levels of IL-12 were measured using an enzyme immunoassay on venous blood samples collected before the immunotherapy and at 1-week intervals. The clinical response consisted of partial response (PR) in four and stable disease (SD) in eight patients, whereas the other seven patients progressed. Mean serum levels of IL-12 observed in the overall patients significantly increased in response to IL-2 injection. Moreover, by evaluating IL-12 variations in relation to the clinical response, a marked significant increase in IL-12 mean values occurred in patients with response or SD, whereas the progressing patients showed a significant decline in IL-12 levels during IL-2 administration. Finally, IL-12 mean pretreatment values observed in patients who progressed were significantly higher than those seen in non-progressing patients. This study shows that low-dose IL-2 immunotherapy of cancer may stimulate the in vivo release of IL-12, and it would suggest that IL-2-induced IL-12 enhancement is associated with a favourable prognosis.     

Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.

On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.     

国产吉西他滨联合顺铂治疗晚期卵巢癌的临床研究

目的:探讨国产吉西他滨(泽菲)联合顺铂治疗晚期卵巢癌的疗效及毒性反应。方法:泽菲1000mg/m2静脉滴注超过30分钟,第1、8天,顺铂30mg/m2静脉滴注超过3小时,第1~3天,化疗前30分钟推注康泉预防消化道反应,每2天重复1次,至少2疗程,治疗至疾病进展或出现不能接受的毒性反应,最多6疗程,每2疗程后评价疗效,复查包括妇科检查、胸腹CT、血CA125。随访30个月。结果:31例转移性卵巢癌共完成疗程数为123个,每个患者接受治疗2~6个疗程,平均4个疗程,随访率100%,获得CR2例,PR13例,有效率48·39%,生存质量明显提高。结论:泽菲联合顺铂对于晚期卵巢癌患者是有效的,毒性反应可以耐受,值得临床进一步研究。     

A randomized study of tamoxifen alone versus tamoxifen plus melatonin in estrogen receptor-negative heavily pretreated metastatic breast-cancer patients

Recent experiments suggest the possibility of modulating the efficacy of cancer endocrine therapy by the pineal hormone melatonin (MLT). In particular, it has been demonstrated that MLT may stimulate estrogen receptor (ER) expression and enhance tamoxifen (TMX) effects other than the antiestrogenic action. Therefore, MLT could amplify the efficacy of TMX also in patients with negative ER. On this basis, a randomized study was performed with TMX versus TMX plus MLT in ER-negative metastatic breast cancer patients, who were unable to tolerate further chemotherapy, because of age, low performance status and/or heavy chemotherapeutic pretreatment. The study included 40 ER-negative post-menopausal, metastatic breast cancer patients, who were randomized to receive TMX alone (20 mg/day orally) or TMX plus MLT (20 mg/day orally in the evening). No complete response was seen. Partial response rate was significantly higher in patients treated with TMX and MLT than in those, who received TMX alone (7/19 vs 2/21, p<0.05). Moreover, the percent of survival at 1 year was significantly higher in patients treated with TMX plus MLT than in those treated with TMX alone (12/19 vs 5/21, p<0.01). No MLT-related toxicity was observed; on the contrary, most patients receiving MLT experienced a relief of anxiety and of depression. This preliminary study suggests that the association of the pineal hormone MLT may make TMX effective also in ER-negative metastatic breast cancer patients.     

Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status

Melatonin (MLT) has been proven to counteract chemotherapy toxicity, by acting as an anti-oxidant agent, and to promote apoptosis of cancer cells, so enhancing chemotherapy cytotoxicity. The aim of this study was to evaluate the effects of concomitant MLT administration on toxicity and efficacy of several chemotherapeutic combinations in advanced cancer patients with poor clinical status. The study included 250 metastatic solid tumour patients (lung cancer, 104; breast cancer, 77; gastrointestinal tract neoplasms, 42; head and neck cancers, 27), who were randomized to receive MLT (20 mg/day orally every day) plus chemotherapy, or chemotherapy alone. Chemotherapy consisted of cisplatin (CDDP) plus etoposide or gemcitabine alone for lung cancer, doxorubicin alone, mitoxantrone alone or paclitaxel alone for breast cancer, 5-FU plus folinic acid for gastro-intestinal tumours and 5-FU plus CDDP for head and neck cancers. The 1-year survival rate and the objective tumour regression rate were significantly higher in patients concomitantly treated with MLT than in those who received chemotherapy (CT) alone (tumour response rate: 42/124 CT + MLT versus 19/126 CT only, P < 0.001; 1-year survival: 63/124 CT + MLT versus 29/126 CT only, P < 0.001). Moreover, the concomitant administration of MLT significantly reduced the frequency of thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis and asthenia. This study indicates that the pineal hormone MLT may enhance the efficacy of chemotherapy and reduce its toxicity, at least in advanced cancer patients of poor clinical status.     

A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients.

Preliminary data would suggest that the pineal hormone, melatonin (MLT), may enhance tamoxifen (TMX) anti-tumour efficacy. Both MLT and TMX have been used as single agents in the palliative treatment of metastatic neoplasms, other than the classical hormone-dependent tumours, without, however, any clear efficacy. On this basis, a phase II study with TMX plus MLT has been performed in untreatable metastatic solid tumour patients. The study included 25 metastatic solid tumour patients other than breast cancer and prostate cancer (six unknown primary tumour; four melanoma; four uterine cervix carcinoma; five pancreatic cancer; three hepatocarcinoma; two ovarian cancer; one non-small-cell lung cancer), for whom no other effective standard therapy was available, because of poor clinical conditions, no response to previous chemotherapies and/or chemotherapy-resistant tumours. Both drugs were given orally every day until disease progression (TMX, 20 mg day-1 at noon; MLT, 20 mg day-1 in the evening). Three patients had a partial response (PR) (12%; 95% confidence limits 2-24%) (one cervix carcinoma; one melanoma; one unknown primary tumour). A stable disease (SD) was achieved in 13 other patients, whereas the remaining nine patients progressed. Performance status (PS) improved in 9/25 patients, whose median score increased from 50% to 70%. Finally, a survival longer than 1 year was observed in 7/25 (28%) patients. This phase II study would suggest that the neuroendocrine combination with TMX plus MLT may have some benefit in untreatable metastatic solid tumour patients, either in controlling cancer cell proliferation or improving the PS.     

A case of advanced gastric cancer responding to combination chemotherapy with low-dose 5-FU plus CDDP

A 56-year-old man presented with dysphagia, and was found to have a type 3 advanced gastric cancer with bilateral multiple lung metastases. This patient was treated with low-dose 5-FU plus CDDP chemotherapy. In the first course, CDDP (6 mg/m2/day) plus 5-FU (300 mg/m2/day) were infused for 5 successive days a week, but a tumor response was not achieved. Therefore, in the second course, CDDP (6 mg/m2/day) plus 5-FU (600 mg/m2/day) were infused every other day (3 days a week). In response to the treatment, both the gastric tumor and the lung metastases almost completely disappeared (reduction rate 95%), and PR was achieved. The CEA level markedly decreased, from 260.3 to 1.4 ng/ml and the patient's symptoms disappeared. Following this treatment, low-dose CDDP plus UFT therapy was performed and the PR was maintained for 12 months. This report shows a case of advanced gastric cancer that responded to low-dose 5-FU plus CDDP.     

Phase I trial of concurrent twice-weekly recombinant human interleukin-12 plus low-dose IL-2 in patients with melanoma or renal cell carcinoma.

PURPOSE: To maintain interferon gamma (IFNgamma) induction by recombinant human interleukin-12 (rhIL-12) and enhance its activity against melanoma and renal cell cancer, a regimen of twice-weekly intravenous (IV) rhIL-12 was modified to include concurrent low-dose subcutaneous (SC) IL-2 in a phase I dose escalation study. PATIENTS AND METHODS: Patients received 6-week cycles of twice-weekly IV rhIL-12 at doses of 300 to 500 ng/kg. Midway through cycle 1, low-dose SC IL-2 was added. The IL-2 was escalated from 0.5 to 6.0 MU/m2. Grade 3 elevations of hepatic ALT, AST, or alkaline phosphatase were not considered dose-limiting unless values were more than 10 times normal. During cycle 1, patients underwent immune monitoring to assess the effect of IL-2 on lymphocyte activation and cytokine production induced by rhIL-12. RESULTS: Twenty-eight patients were enrolled onto the study. The maximum-tolerated dose (MTD) was 500 ng/kg rhIL-12 plus 3 MU/m2 IL-2. Toxicities related to the addition of IL-2 at the MTD included fever or chills, anemia, fatigue, nausea or vomiting, and orthostatic hypotension. At the MTD, IL-2 significantly augmented IFNgamma and IFNgamma-inducible protein-10 production by rhIL-12 and led to a three-fold expansion of natural killer cells. There was one major clinical response (partial response) as well as two pathologic responses; all occurred in melanoma patients. Stable disease for three to six cycles was only observed at or above the MTD in melanoma and renal cell cancer patients. CONCLUSION: The addition of concurrent low-dose IL-2 to rhIL-12 is well tolerated, restores and maintains immune activation by rhIL-12, and has clinical activity. This regimen should be further investigated in phase II studies in untreated patients with melanoma or renal cell cancer and in other rhIL-12-responsive malignancies.     

伊立替康联合氟尿嘧啶/亚叶酸钙方案一线治疗37例晚期大肠癌

背景与目的：伊立替康联合氟尿嘧啶／亚叶酸钙方案为晚期大肠癌一线治疗的标准方案。本研究观察伊立替康联合氟尿嘧啶／亚叶酸钙双周（CPT—11＋5FU／LV双周FOLFIRI）方案一线治疗晚期大肠癌的客观有效率及不良反应。方法：2001年5月-2005年3月，37例晚期大肠癌患者接受FOLFIRI方案一线治疗。化疗剂量为CPT—11 180mg／m^2静脉点滴第1天，亚叶酸钙（LV）200mg／m^2静脉点滴第1、2天，5．FU400mg／m^2静推第1、2天，5-FU600mg／m^2持续泵注44小时第1、2天，14天为1周期。结果：36例可评价疗效患者有效率为41。7％。Ⅲ／Ⅳ度骨髓抑制发生率占总人数的35．1％和8．1％，4例患者出现中性粒细胞减少性发热。Ⅲ度迟发性腹泻发生率为8．1％：结论：伊立替康联合氟尿嘧啶／亚叶酸钙双周方案（FOLFIRI）是一线治疗晚期大肠癌安全而有效的方案。     

Preliminary clinical evaluation of low-dose CDDP and continuous 5-FU therapy for advanced gallbladder cancer

5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. Low-dose cisplatin (CDDP) and continuous venous infusion of 5-FU have recently shown additive or synergistic antitumor effects in experimental models. In this study, we evaluated the clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gallbladder cancer. From December, 1993 to June, 1998, 13 patients with advanced gallbladder cancer were treated with low-dose FP therapy. Patients were eligible for this study if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for one hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks according to response and tolerance. Low-dose FP therapy was given to 12 patients (92.3%). The response rate was 66.7% and the median survival time was 151 days. The regimen was tolerable, with the most common toxicity being nausea (38.5%). There were no severe side effects except for one patient who suffered from grade 3 nausea. We conclude that low-dose FP therapy may be useful as a palliative chemotherapy for cases of advanced gallbladder cancer.     

紫杉醇联合卡铂治疗晚期非小细胞肺癌的临床观察

目的:评价紫杉醇联合卡铂化疗方案治疗晚期非小细胞肺癌的近期疗效和不良反应.方法: 25例晚期非小细胞肺癌,应用紫杉醇150mg-175mg/m2、卡铂按浓度/时间曲线下面积(AUC)＝5给药联合化疗,每3周重复,进行3-4周期.结果: 全组CR 0例,PR 12例,SD 10例,PD 3例,总有效率48 %,不良反应主要为关节肌肉酸痛、骨髓抑制、轻度胃肠道反应、脱发.结论: 紫杉醇联合卡铂治疗晚期非小细胞肺癌疗效较好,不良反应可耐受,有较好的临床应用价值.     

紫杉醇联合奥沙利铂和卡培他滨治疗晚期胃癌的临床观察

目的　评价紫杉醇联合奥沙利铂和卡培他滨（ＰＯＸ方案）治疗晚期胃癌的疗效和不良反应。方法　２１例晚期胃癌患者均采用ＰＯＸ方案治疗：紫杉醇８５ｍｇ／ｍ^２,第１、８天,静脉滴注;奥沙利铂１３０ｍｇ／ｍ２,第１天,静脉滴注;卡培他滨１０００ｍｇ／ｍ^２分２次口服,第１～１４天,２１天为１周期。２周期评价疗效。结果　全组２１例均可评价疗效,其中ＰＲ１３例,ＳＤ６例,ＰＤ２例,客观有效率为６１.９％;中位肿瘤进展时间为５.７个月,中位总生存期为１１个月。不良反应主要为骨髓抑制、恶心呕吐和外周神经毒性。结论　紫杉醇联合奥沙利铂和卡培他滨治疗晚期胃癌疗效较好,不良反应可耐受,值得临床进一步研究。