Biomedical subjects

F Paolorossi

Publications and source records attributed to F Paolorossi.

At least 19 recordsLinked to original sources

PubMed2000

Five-year survival results of subcutaneous low-dose immunotherapy with interleukin-2 alone in metastatic renal cell cancer patients.

After the discovery of its essential role in anticancer immunity, IL-2 cancer immunotherapy has shown that comparable results may be obtained with different schedules, including intravenous high-dose IL-2 as a bolus or as a 24-hour intravenous infusion or prolonged subcutaneous injection of low-dose IL-2 with or without IFN-alpha. This study shows the long-term results obtained in 92 metastatic renal cell cancer (RCC) patients with low-dose subcutaneous IL-2, which was given at 3 million IU twice/day for 5 days/week for 6 consecutive weeks. In nonprogressing patients, a second cycle was planned after a 21-day rest period, followed by maintenance therapy consisting of 5 days of treatment every month until disease progression. Complete response (CR) was achieved in only 2/92 (2%) patients, and partial response (PR) was observed in 19 patients (21%). Therefore, the response rate (CR + PR) was 21/92 (23%), with a median duration of response of 25 months. Stable disease (SD) occurred in 37 patients (40%), whereas the other 34 (37%) had a progressive disease (PD). The response rate was significantly higher in patients with a disease-free interval of >1 year than in those with a lower interval, in patients with a high performance status (PS) than in those with a low PS, and in patients with sites of disease other than the liver. A 5-year survival was obtained in 9/92 (9%) patients, and the percent of survival was significantly higher in patients with a response or SD than in those with PD. The treatment was well tolerated in all patients. This study confirms that low-dose subcutaneous IL-2 alone in an effective and well tolerated therapy of metastatic RCC, with results comparable to those described with more aggressive and toxic IL-2 schedules.

Adult↗

PubMed1999

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.

Adult↗

PubMed1999

Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study.

Thrombocytopenia is a frequent complication of cancer and constitutes an absolute contraindication for chemotherapy. Recent studies have demonstrated that platelet generation may be influenced by both cytokines and neurohormones. In particular, the pineal indole melatonin has been proven to enhance platelet number in patients with thrombocytopenia due to different reasons. On this basis, we have evaluated the effects of a concomitant administration of melatonin in thrombocytopenic cancer patients undergoing chemotherapy. The study was performed in 14 metastatic breast cancer women treated by weekly epirubicin. Each cycle consisted of epirubicin at 25 mg/m2 i.v. at weekly intervals. Melatonin was given orally at 20 mg/day in the evening every day, starting 7 days prior to chemotherapy. Patients were considered as evaluable when they received at least four cycles of chemotherapy. Evaluable patients were 12/14. The induction phase with melatonin induced a normalization of platelet number in 9/12 evaluable patients, and no further platelet decline occurred in chemotherapy. Objective tumor regression was achieved in 5/12 (41%) patients. This preliminary study would suggest that melatonin may be effective in the treatment of cancer-related thrombocytopenia and to prevent chemotherapy-induced platelet decline. Until now, melatonin therapy of cancer has been generally considered as an alternative treatment to chemotherapy. In contrast, this study would suggest that melatonin may contribute to the realization of chemotherapy in metastatic cancer patients unable to tolerate the chemotherapeutic approach because of persistent thrombocytopenia.

Adult↗

PubMed1997

Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin.

Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.

Adult↗

PubMed1997

A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state.

Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage. In addition, melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production. On this basis, we have performed a randomized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients (NSCLC) with poor clinical status. The study included 70 consecutive advanced NSCLC patients who were randomized to receive chemotherapy alone with cisplatin (20 mg/m2/day i.v. for 3 days) and etoposide (100 mg/m2/day i.v. for 3 days) or chemotherapy plus melatonin (20 mg/day orally in the evening). Cycles were repeated at 21-day intervals. Clinical response and toxicity were evaluated according to World Health Organization criteria. A complete response (CR) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone. Partial response (PR) occurred in 10/34 and in 6/36 patients treated with or without melatonin, respectively. Thus, the tumor response rate was higher in patients receiving melatonin (11/34 vs. 6/35), without, however, statistically significant differences. The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15/34 vs. 7/36, P < 0.05). Finally, chemotherapy was well tolerated in patients receiving melatonin, and in particular the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group. This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy, mainly in terms of survival time, and reduce chemotherapeutic toxicity in advanced NSCLC, at least in patients in poor clinical condition.

Adult↗

PubMed1997

[Immunotherapy for metastatic renal carcinoma with interleukin-2 in a subcutanous administration schedule of short duration. Subcutaneous IL-2 in renal carcinoma].

It has been shown that low-dose subcutaneous (SC)IL-2 exerts an efficacy similar to that described for the intravenous high-doses in the immunotherapy of metastatic renal cell cancer (RCC). However, it remains to be established which could be the optimal duration of treatment. The most common schedules with subcutaneous IL-2 are generally consisting of 6 weeks of therapy, with an IL-2 dose of about 6 million IU/day. This study was performed to evaluate the efficacy of IL-2 subcutaneous immunotherapy with a duration of 4 weeks only. The study included 13 evaluable metastatic RCC patients. IL-2 has been injected subcutaneously at 6 million IU/day for 6 days/week for 4 weeks, by repeating a second cycle in nonprogressing patients after a 21-day rest period. Objective tumor regressions were achieved in 3/13 (23%) patients consisting of CR in 1 and PR in the other 2. Stable disease was obtained in other 6 patients. This preliminary study would suggest that a shorter dose-matched S.C.IL-2 immunotherapy may have a similar therapeutic efficacy in metastatic RCC. Therefore, the 4-week IL-2 S.C. immunotherapy, instead of the 6-week schedule could become the standard immunotherapeutic schedule, with following decreased cost and toxicity.

Adult↗

PubMed1996

Is there a role for melatonin in the treatment of neoplastic cachexia?

It is known that neoplastic cachexia shows metabolic characteristics different from other common causes of malnutrition, and that it is mainly due to an abnormal secretion of TNF, whose levels are often high in patients with advanced neoplasia. Previous clinical studies have suggested that the pineal hormone melatonin (MLT), which plays an essential role in the neuroendocrine regulation of biological systems, may improve the clinical status of advanced cancer patients and inhibit TNF secretion. To investigate the relationship between MLT, TNF and cancer-related weight loss, 100 untreatable metastatic solid tumour patients entered this study to receive either supportive care alone, or supportive care plus MLT (20 mg/day orally in the evening). Patients were observed for 3 months, and were considered evaluable when they were observed for at least 2 months. There were 86 evaluable patients, the other 14 patients having died from rapid progression of disease. The per cent of weight loss greater than 10% was significantly higher in patients treated by supportive care alone than in those concomitantly treated by MLT, with no difference in food intake (P < 0.01). Mean serum levels of TNF progressively increased in the supportive care group, but to levels that were not significantly different from pretreatment values. In contrast, TNF mean concentrations significantly decreased (P < 0.05) in patients concomitantly treated by MLT. These results suggest that the pineal hormone MLT may be effective in the treatment of the neoplastic cachexia by decreasing TNF blood concentrations.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

The pineal hormone melatonin in hematology and its potential efficacy in the treatment of thrombocytopenia.

Recent experimental studies suggested that hematopoietic cell proliferation and differentiation are under a neuroendocrine control and that they change in relation to the 24-hour period. Moreover, it has been shown that the pineal hormone melatonin (MLT) plays a role in mediating the influence of the psychoendocrine system and of the lighting conditions on the hematopoiesis. Finally, MLT has appeared to regulate hematopoietic cell growth by influencing apoptosis-related mechanisms. In particular, preliminary studies have shown that the pineal hormone MLT may determine some benefits in blood cell disorders, mainly platelet diseases. On this basis, a pilot phase II study of MLT therapy was performed in patients suffering from persistent thrombocytopenia due to different causes. The study included 14 patients, and thrombocytopenia was due to bone metastatic involvement in 5, hypersplenism in 3, myelodysplastic syndrome in 3, DIC in 1, genetic factors in 1, and Werlhof's disease in the last case. MLT was given orally at 20 mg/day in the evening for 2 months. No MLT-related toxicity occurred. A normalization of platelet number was achieved in 8/14 (57%), and platelet mean number significantly increased on MLT therapy. This preliminary study would suggest that MLT may be effective in the treatment of thrombocytopenia due to different reasons, for which no effective standard therapy is available.

Adolescent↗

PubMed1994

A randomized study of immunotherapy with low-dose subcutaneous interleukin-2 plus melatonin vs chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small cell lung cancer.

AIMS AND BACKGROUND: The therapeutic role of chemotherapy in advanced non-small cell lung cancer (NSCLC) is controversial because of its potentially detrimental action on host anticancer defenses. On the contrary, IL-2 would seem to prolong survival time by improving the immune status, even though it is generally less effective in determining tumor regression in NSCLC. Our previous studies have suggested the possibility of increasing tumor sensitivity to IL-2 by concomitant administration of immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On this basis, a study was carried out to evaluate the efficacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC. METHODS: The study included 60 patients with locally advanced or metastatic NSCLC, who were randomized to receive immunotherapy or chemotherapy. The immunotherapy consisted of IL-2 (3 million IU/day subcutaneously for 6 days/week for 4 weeks) and MLT (40 mg/day orally every day, starting 7 days before IL-2); in nonprogressing patients, a second cycle was repeated after a 21-day rest period, then they underwent a maintenance period consisting of one week of therapy every month until progression. Chemotherapy consisted of cisplatin (20 mg/m2) and etoposide (100 mg/m2)/day intravenously for 3 days; cycles of chemotherapy were repeated every 21 days until progression. RESULTS: No complete response was obtained. A partial response was achieved in 7/29 patients treated with chemotherapy and in 6/31 patients receiving chemotherapy. The difference was not significant. In contrast, the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy. Toxicity was substantially lower in patients receiving immunotherapy than in those given chemotherapy. CONCLUSIONS: This randomized study showed that immunotherapy with low-dose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patients affected by advanced NSCLC.

Adult↗

PubMed1993

A weekly schedule of epirubicin in pretreated advanced breast cancer.

AIMS: Epirubicin is an analogue of doxorubicin with a similar activity but less toxicity. The aim of this study was to evaluate the efficacy and the tolerability of a weekly schedule of epirubicin. METHODS: Fifty-three patients with metastatic breast cancer, pretreated and/or with a low performance status, were treated with 25 mg/m2/week of the drug. RESULTS: Of the 49 evaluable patients, 3 achieved a complete response (6.1%) and 21 a partial response (42.8%) with a median duration of 6.3 months. Median survival was significantly higher in responders than in nonresponders: 15.2 vs 6.0 months (P < 0.005). Furthermore, a marked improvement in performance status was observed (ECOG scale). No cardiologic toxicity was observed, and gastrointestinal toxicity was low. CONCLUSIONS: Epirubicin administered weekly represent a valid alternative to conventional treatments.

Adult↗

PubMed1993

Respiratory distress syndrome in patients with advanced cancer treated with pentoxifylline: a randomized study.

The inappropriate endogenous secretion of tumour necrosis factor (TNF) could play a role in the pathogenesis of acute respiratory distress syndrome (ARDS), one of the most frequent causes of death in cancer patients. Because of its capacity to inhibit TNF secretion in vitro, pentoxifylline (PTX) could be extremely useful in ARDS therapy. In this study 30 advanced cancer patients with ARDS were randomized to receive either the conventional care or conventional care plus PTX (100 mg i.v. twice a day for 7 days followed by an oral administration of 400 mg three times a day) to evaluate the efficacy of PTX in reducing TNF serum levels and in improving the symptoms of this syndrome. Serum levels of TNF were measured before and after 7 days of therapy. The percentage of patients alive at 7 days was significantly higher in the PTX-treated group than in the controls (12/15 versus 3/15; P < 0.001). The mean survival time was significantly higher in the PTX-treated group than in the controls. A clinical and/or radiological improvement was obtained in 11/15 patients treated with PTX and in only 2/15 patients in the conventional care group (P < 0.01). TNF mean levels significantly decrease in the PTX-treated group. These data confirm in vivo the capacity of PTX to inhibit TNF secretion in patients with ARDS. Moreover PTX therapy may improve the symptoms related to ARDS without particular toxic effects.

Administration, Oral↗

PubMed1992

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.

Adult↗

PubMed1992

Intracavitary administration of interleukin-2 as palliative therapy for neoplastic effusions.

Cytokines have recently appeared to be effective in the palliative therapy of neoplastic effusions. The present study was carried out to evaluate the efficacy and the tolerability of an intracavitary injection of IL-2 in patients with neoplastic effusion due to solid tumors. The study included 14 patients with cytologically positive effusion (pleura, 11; peritoneum, 2; pericardium, 1). Tumor histotypes were: mesothelioma, 5; non-small cell lung cancer, 3; breast cancer, 2; ovarian cancer, 2; cervix carcinoma, 1; unknown primary tumor, 1. The efficacy was evaluated according to the criteria of Paladine et al. (Cancer 38: 1903, 1976). An objective response was achieved in 10/14 (71%) patients (4 CR, 6 PR), with a median duration of 4 months (range, 2-8). No important toxicity was seen. This preliminary study showed that low dose IL-2 given intracavitarily is an effective and well-tolerated therapy in patients with neoplastic effusions.

Adult↗

PubMed1992

Second line therapy with low-dose subcutaneous interleukin-2 alone in advanced renal cancer patients resistant to interferon-alpha.

Interleukin-2 (IL-2), given subcutaneously with interferon-alpha, induces clinical results similar to those achieved with intravenous administration in advanced renal cancer but with lower toxicity. This study was performed to investigate the efficacy of IL-2 subcutaneous therapy alone in advanced renal cancer patients pretreated with interferon-2 alpha. The study included 13 evaluable patients, 6 of whom had visceral metastasis sites. The cycle consisted of IL-2 at 9 x 10(6) IU/m2 twice daily for 2 days, followed by 1.8 x 10(6) IU/m2 every 12 h for 5 days/week for 6 weeks. Clinical responses were: partial response: 4(31%); stable disease: 7(54%), progressive disease: 2(15%). The median duration of response was 9+ months (range 6(+)-12+). Toxicity was low in all patients, and in particular no important cardiovascular side-effect was seen. The results of this study show that IL-2 subcutaneous therapy alone is an effective and well tolerated treatment in advanced renal cancer patients progressed under interferon-alpha therapy.

Adenocarcinoma↗

PubMed1992

Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin.

At present, there is no effective medical therapy in metastatic nonsmall cell (NSC) lung cancer patients who progressed under a first-line chemotherapy containing cisplatin. Since recent data have demonstrated the antineoplastic properties and the lack of toxicity of the pineal hormone melatonin (MLT), a randomized study was designed to evaluate the influence of an MLT treatment (10 mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients, who did not respond to a first-line chemotherapy containing cisplatin. The study includes 63 consecutive metastatic NSC lung cancer patients, who were randomized to receive MLT (n = 31) or supportive care alone (n = 32). The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care. No drug-related toxicity was seen in patients treated with MLT, who, on the contrary, showed a significant improvement in performance status. This randomized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSC lung cancer patients who progressed under a first-line chemotherapy with cisplatin, for whom no other effective therapy is available up to now.

Adult↗

PubMed1991

Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response.

Mitoxantrone (DHAD), an anthracenedione with antineoplastic properties similar to doxorubicin, was tested for therapeutic efficacy and for immunomodulating action on lymphocyte subsets in 16 metastatic breast cancer patients, 12 of whom had been previously treated with chemotherapy. DHAD was given intravenously at a dose of 14 mg/m2 every 21 days. To evaluate total T lymphocytes (CD3), T helper (CD4), and T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio, venous blood samples were drawn before and after the first DHAD cycle. Moreover, in 8/16 patients, B lymphocytes (CD20), T suppressor cells (CD8+/CD57+), T cytotoxic cells (CD8+/CD57-), NK (CD16) and IL-2 receptor-expressing cells (CD25) were also measured at the same time. An objective tumor response was achieved in 5/16 (31%) patients and the response rate was significantly higher in patients pretreated with hormone therapy alone than in those pretreated with chemotherapy. No relation was found between clinical response and changes in the CD4/CD8 ratio. Neither the mean number nor the percentage of CD3, CDA and CD8 cells observed after DHAD were significantly different with respect to those seen before. In contrast, the mean number of T suppressor cells, B lymphocytes and CD25-positive cells was significantly lower after than before DHAD administration, whereas no difference was seen in NK cells. These results confirm in humans the immunomodulating properties of DHAD previously described in experimental conditions. However, the DHAD-induced changes in lymphocyte subsets do not seem to be related to the clinical response in breast cancer.

Adult↗

PubMed1990

A study of the pineal hormone melatonin as a second line therapy in metastatic colorectal cancer resistant to fluorouracil plus folates.

Since there is no effective second line chemotherapy in colorectal cancer resistant to fluorouracil, this study was carried out to evaluate the therapeutic activity of the pineal hormone melatonin, which has appeared to have antineoplastic activity in some experimental conditions, in patients with metastatic colorectal carcinoma who did not respond to fluorouracil. The study included 14 patients (8 men, 6 women; mean age 58 years). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; after that, melatonin therapy was continued at 10 mg/day orally in responder patients, in those with stable disease and/or an evident improvement in PS. One patient had a minor response; 3 other patients had a stable disease, whereas the other 10 cases progressed. An evident improvement in PS was seen in 5/14 (36%) patients. These preliminary results show that melatonin does not have important antitumor activity in metastatic colorectal cancer patients resistant to fluorouracil. However, the pineal hormone could be usefully employed as supportive care to improve the quality of life in these patients for whom no standard treatment is yet available.

Adult↗