Phase II trial of 13-cis retinoic acid plus interferon-alpha in advanced squamous cell carcinoma of head and neck, refractory to chemotherapy.
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Adolescent↗
Biomedical subjects
G Catalano
Publications and source records attributed to G Catalano.
Toxicity and therapeutic response to chemotherapy in patients aged 70 years or older with advanced cancer.
To evaluate the impact of chemotherapy in terms of feasibility and activity in elderly patients, we treated 120 patients aged 70 years or older with advanced cancer in six major organ sites (breast, colorectum, lung, stomach, ovary, and head and neck). Furthermore, we compared the results in this age group with those in 120 patients with similar clinical features receiving the same chemotherapeutic combinations but whose age was under 70. Our results show that chemotherapeutic regimens routinely used in younger patients yield the same benefits and levels of toxicity in older patients. In none of the different organ sites, in fact, did we observe a higher incidence or severity of side effects, nor were there differences in response rate and survival. In conclusion, elderly cancer patients who are not suffering from medical complications, which are generally increased in aged patients (e.g., cardiovascular, pulmonary, renal, or neurological diseases), can be considered candidates for full doses of chemotherapy, like their younger counterparts.
Activities of Daily Living↗
Different doses of granulocyte colony stimulating factor to support a weekly chemotherapeutic regimen in advanced gastric cancer: a randomized study.
It was our intention to verify if increases of granulocyte colony stimulating factor (G-CSF) dose were able to reduce treatment delays due to leukopenia in our weekly regimen of cisplatin (40 mg/m2), epidoxorubicin (35 mg/m2), 6S-leucovorin (250 mg/m2) and 5-fluorouracil (500 mg/m2), usually supported by G-CSF at a dose of 5 mu g/kg. Forty five patients with advanced gastric carcinoma (30 males and 15 females; median age 64 years) were randomized to receive three different doses of G-CSF (5, 8 and 10 mu g/kg) by s.c. injection. We did not observe any difference in the mean value of neutrophil counts at each of the 8 weeks of treatment; while we registered a higher incidence of severe neutropenia (< 500/mm3) in patients receiving higher G-CSF doses: two patients in the group at 5 mu g/kg, four in the group at 8 mu g/kg and seven in the group at 10 mu g/kg. Furthermore, low doses of G-CSF allowed a similar number of chemotherapeutic administrations in the eight study weeks. The results arising from our study do not seem to support the use of higher doses of G-CSF, at least in not such a weekly regimen.
Adult↗
A phase I trial of 5-fluorouracil, leucovorin and interferon-alpha 2b administered by 24 h infusion in metastatic colorectal carcinoma.
A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN) was conducted in 15 advanced colorectal cancer patients refractory to a bolus regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600 mg/m2 administered concomitantly with LV at 500 mg/m2 over a 24 h period. IFN-alpha 2b was administered by 24 h infusion from the second cycle at escalating dose (4.5, 9, 18 and 27 MU/m2). The maximum tolerated dose of IFN was 18 MU/m2. At 27 MU/m2 two patients complained of diarrhea grade 3, so that the escalation of IFN dose was stopped. Two patients achieved a partial response (IFN level dose 9-18 MU/m2). Eight patients had stable disease. Pharmacokinetics of 5-FU were not influenced by IFN at any level dose. Our results show that doses of IFN of 18 MU/m2 given by a 24 h infusion can be administered safely to an established and active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been planned to define the level of activity of this regimen.
Adult↗
Tardive dyskinesia as a result of long-term prochlorperazine use.
Prochlorperazine is a centrally acting dopamine receptor antagonist that is most commonly used for the treatment of nausea and vomiting. Like many dopamine antagonists, prochlorperazine has the ability to induce extrapyramidal reactions in susceptible patients. Rarely, however, have cases of tardive dyskinesia been caused by the long-term use of this agent. We report the case of a patient who used prochlorperazine for a prolonged period and, during hospital admission, was found to have a new movement disorder. Alternative antiemetics that do not pose a risk of movement disorders, such as ondansetron and granisetron, are readily available and are efficacious.
Antiemetics↗
Meperidine associated mental status changes in a patient with chronic renal failure.
Meperidine is widely used for pain control in the hospital setting. It is also known for its propensity to cause mental status changes in renally and hepatically impaired patients. A case is reported of a 37-year-old man with chronic renal failure maintained on peritoneal dialysis in whom delirium developed when he was treated with meperidine not only on one occasion but also on two subsequent admissions. The pharmacology of meperidine is reviewed and the implications of using the medication in patients with renal impairment are discussed.
Adult↗
Have enteric infections a role in 5-fluorouracil-associated diarrhea?
In 16 advanced colorectal cancer patients with 5-fluorouracil-associated diarrhea, we evaluated the role of bacterial pathogens in the development of this adverse effect. Neither Clostridium difficile nor other pathogens were cultured from fecal specimens. These data seem to suggest that it is unlikely that intestinal infections have a role in the pathogenesis of 5FU-associated diarrhea.
Adult↗
A randomised trial of octreotide vs best supportive care only in advanced gastrointestinal cancer patients refractory to chemotherapy.
Octreotide, a somatostatin analogue, has been shown to inhibit the growth of gastrointestinal cancers in vitro and in vivo. To assess the anti-tumour effect of octreotide, we performed a randomised trial comparing octreotide with best supportive care in advanced gastrointestinal cancer patients refractory to chemotherapy. A total of 107 patients with advanced gastrointestinal cancer refractory to chemotherapy were randomised to receive octreotide at the dose of 200 micrograms three times a day for 5 days a week, or the best supportive care only. The primary outcome variable was the survival duration. Response rate was an outcome variable of secondary importance. Fifty-five patients (15 stomach, 16 pancreas, 24 colon-rectum) received octreotide, while 52 (14 stomach, 16 pancreas, 22 colon-rectum) received the best supportive care. Patients treated with octreotide had a significant advantage in duration of survival with a median survival time of 20 weeks vs 11 in the control group (P < 0.0001). This advantage was present also considering the survival data for each tumour group. Twenty-five patients (45%) given octreotide showed stable disease vs only eight (15%) in the control group (P < 0.001). In conclusion, octreotide therapy seems to confer a survival benefit in advanced gastrointestinal cancer patients refractory to chemotherapy. Additional studies will be needed to confirm these results and to clarify other questions about dose and schedule of octreotide.
Adult↗
Escalating dose of tegafur combined with oral etoposide in metastatic gastric carcinoma.
Fifteen patients with advanced gastric cancer received orally etoposide 100 mg daily for 14 days and escalating doses of tegafur. The starting dose was 400 mg daily. The maximum tolerated dose of tegafur was identified at 850 mg daily. Unacceptable toxicity was seen at 1000 mg, and consisted of diarrhea, stomatitis and leukopenia. Two partial responses were seen at 800 mg daily. In conclusion, our data show that etoposide and tegafur can be safely administered in combination by the oral route.
Aged↗
Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.
PURPOSE: We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity. PATIENTS AND METHODS: Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment. RESULTS: At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH. CONCLUSION: This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.
Aged↗
[The ethical aspects of human experimentation].
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Acquired Immunodeficiency Syndrome↗
Factitious disorder presenting as bacteremia. Case report and literature review.
A factitious disorder is typically a chronic illness that can be frustrating for the clinical team because it often eludes early diagnosis. Case reports in the literature show that patients can simulate almost any illness or disease state with some resorting to injecting themselves with contaminated substances to produce infection. A case is reported of a patient with self-induced bacteremia who presented with multiple episodes of polymicrobial bloodstream infections. The various types of factitious disorders and a review of treatment options are discussed. The current criteria for factitious disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) 4th edition are reviewed.
Adult↗
A pilot clinical trial of surgical adjuvant treatment with high-dose 6S-leucovorin/5-fluorouracil and radiation therapy for high-risk rectal carcinoma.
AIMS AND BACKGROUND: The study was performed to evaluate the feasibility of combining leucovorin (LV) with 5-fluorouracil (5FU) and radiation therapy as adjuvant treatment for high-risk rectal carcinoma. METHODS: Twenty-five patients with histologically proven adenocarcinoma of the rectum, at high-risk of recurrence after potentially curative resection (T3 NO, T and N1-2; MO), received 5FU (370 mg/m2) and 6S-LV (100 mg/m2) on days 1-5, 4 and 8 weeks after surgery. On treatment day 64, radiotherapy on the pelvis (50 Gy) was initiated. Finally, three further courses of 5FU/LV were given at intervals of 4 weeks beginning 28 days after the completion of radiotherapy. RESULTS: The treatment was generally well tolerated. We observed only 2 cases of grade III toxicity (diarrhea) during the third cycle of chemotherapy. No severe complications were recorded following the use of radiotherapy. The mean overall 5FU dose intensity was 92%. After a median follow-up of 24 months, 4 patients had relapsed (liver, lung, and pelvis, 2 cases). CONCLUSIONS: The association of LV to 5FU and radiation therapy seems to be feasible, with acceptable toxicity. The advantage of this combination, in terms of recurrence rate and survival with respect to 5FU/radiotherapy alone, will have to be evaluated in randomized trials.
Adult↗
Hepatocyte growth factor and macrophage inflammatory protein 1 beta: structurally distinct cytokines that induce rapid cytoskeletal changes and subset-preferential migration in T cells.
T-cell migration into tissue depends on a cascade of rapid and selective adhesive interactions with endothelium. "Triggering" is a step in that cascade required to activate T-cell integrins. Hepatocyte growth factor (HGF) may be a physiologically relevant trigger, since we demonstrate that HGF can induce both adhesion and migration of human T-cell subsets and can be detected immunohistochemically on inflamed endothelium. HGF preferentially induces responses from T cells of memory phenotype, in contrast to macrophage inflammatory protein 1 beta (MIP-1 beta), a chemokine which acts preferentially on naive cells. HGF, like the chemokines, binds to heparin, and HGF retained in extracellular matrix is efficient in promoting migration. Further, both MIP-1 beta and HGF induce actin polymerization within seconds, kinetics that approach those required to contribute to physiologic triggering. HGF is a member of a structural family distinct from the chemokines, whose only known receptor is the tyrosine kinase c-Met. HGF induces tyrosine phosphorylation on T cells apparently via a distinct receptor, since no c-Met is detectable by surface staining, PCR, or anti-phosphotyrosine immunoprecipitation. Thus, promotion of T-cell adhesion and migration are previously undescribed functions of HGF that we propose are relevant to selective T-cell recruitment.
Cell Adhesion↗
Etoposide, leucovorin, 5-fluorouracil and interferon alpha-2b in elderly gastric cancer patients: a pilot study.
A total of 23 advanced gastric cancer patients older than 65 years received 500 mg/m2 5-fluorouracil i.v. on days 2-4, 120 mg/m2 vepesid i.v. on days 2-4, 150 mg/m2 6S-leucovorin on days 2-4, and 5 MU/m2 interferon alpha-2b on days 1-5, with cycles being repeated every 3 weeks. Toxicity was severe at an interferon (IFN) dose of 5 MU/m2; only one patient tolerated this dose. In 18 patients an IFN dose of 3 MU/m2 and in 3 other patients a dose of 4 MU/m2 could be given without producing toxicity. At an IFN dose of 5 MU/m2 the most common toxicities encountered were stomatitis (grade 4 in 1 patient and grade 3 in 12 patients), leukopenia (grade 4 in 1 patient and grade 3 in 5 patients), and thrombocytopenia (grade 3 in 3 patients). Two patients achieved a complete response and eight showed a partial response, resulting in an overall response rate of 45% [95% confidence interval (CI), 25%-64%]. The median survival was 7 months for all patients and 9 months for responding patients. In conclusion, without substantially increasing the toxicity, IFN can be added to the etoposide/leucovorin/5-fluorouracil combination, at a dose of 3 MU/m2. To verify the possible enhancement by IFN of the activity of this combination, a randomized trial is under way.
Adenocarcinoma↗
Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis.
Recently, a randomised study demonstrated the utility of oral cooling (cryotherapy) in the prevention of 5-fluorouracil (5FU)-induced stomatitis. In order to verify these results a confirmatory study, using identical treatment regimen, was initiated. 84 patients treated with a 5-FU-containing regimen were randomised to a control arm or to receive oral cryotherapy. End point evaluation was obtained by a global assessment of the physician's judgement and patients' description of mucositis severity graded 0-4. Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy (the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group, P < or = 0.05) and all the chemotherapeutic courses (the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group, P < or = 0.05). In conclusion, the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens.
Adult↗
Bag Surgery as Part of a Protocol to Treat Ovarian Masses by Laparoscopy
In a protocol to treat all ovarian masses endoscopically the major objection is that there are reports that even if the preoperative examinations are favorable there is still a chance as high as 2 to 6% of encountering a malignant proliferation within the cyst, necessitating a conversion to laparotomy within the same operating session. Using the following selection criteria: Premenopausal patients less than 45 years; uni-locular cysts on ultrasound or slightly septated; size of the cyst between 4 and 10 cm; benign characteristics on ultrasound; normal biochemistry, including CA 125, ESR, liver enzymes; and cysts resistant to therapy at least for 6 weeks, we have used the bags whenever the macroscopic aspect of the cyst appeared suspicious for malignancy to the surgeon. The tumor was first fully inserted in the Endo pouch (Autosuture-US Surgical) and then transected from its pedicle. We used bipolar coagulation and scissors. The bag was then brought to the abdominal wall and a minilaparotomy of 5 cm on average was performed. The bag was brought into the opening, the sac opened with scissors, the plastic spread on the skin and only then the tumor was treated inside the bag. Using this technique we did not experience any spread in the abdomen as the laparoscope remained in place and the bag prevented the pneumoperitoneum from deflating.
Journal Article↗
Cisplatin, 5-fluorouracil and interferon alpha 2b for recurrent or metastatic head and neck cancer.
On the basis of preclinical data suggesting the possibility of maximising the efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at 1,000 mg m-2 by continuous infusion for 5 days. Interferon alpha 2b was administered at the dose of 3 million U i.m. daily for 7 days, beginning the day before chemotherapy. Courses were repeated every 3 weeks. Two patients achieved a complete remission, six a partial response, 14 had stable disease and 12 progressed on therapy, for an overall response rate of 23% (95% confidence interval 10-36%). Median survival time was 5 months. Toxicity was severe. Stomatitis, diarrhoea and myelosuppression were the most common side-effects. Because of the poor response rate and the presence of severe toxicity, in our opinion further clinical trials in head and neck cancer should be attempted only after a better definition in preclinical studies of interactions among 5-fluorouracil, cisplatin and interferon.
Adult↗