Is there a standard chemotherapeutic strategy in colorectal cancer?
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
A Zaniboni
Publications and source records attributed to A Zaniboni.
Photic reflex myoclonus: a neurophysiological study in progressive myoclonus epilepsies.
PURPOSE: To investigate the neurophysiological features of photic reflex myoclonus (PRM) in patients with progressive myoclonus epilepsies (PMEs) of different types (Unverricht-Lundborg disease, Lafora's disease, cryptogenic). METHODS: All patients underwent computerized video-polygraphic recordings, collecting electromyographic (EMG) activity from several cranial and limb muscles. PRM was elicited by intermittent photic stimulation (IPS). RESULTS: IPS could evoke PRM with a 1:1 relation at frequencies up to 12 Hz. Back-average of the EEG, triggered from the onset of PRM at the upper limbs, showed a contralateral positive-negative transient in central region, preceded by approximately 10 ms by a similar, ipsilateral occipital wave. When IPS induced bilateral jerking, a time lag of approximately 10 ms between the homologous muscles of the two sides was observed, paralleled by a similar delay between the associated contralateral EEG transients in the two central regions, suggesting spread of cortical myoclonic activity from one hemisphere to the other via transcallosal fibers. PRM propagated in different cranial and limb muscles according to a rostrocaudal pattern, with latencies compatible with a transmission along fast-conducting corticospinal motor pathways. CONCLUSIONS: In our PME patients, PRM presented uniform neurophysiological features, indicating the participation of both occipital and motor cortices, with bilateral spread presumably mediated by transcallosal connections and propagation down the spinal cord via fast-conducting corticospinal pathways.
Adolescent↗
GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.
BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. METHODS: The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. CONCLUSIONS: Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated, effective 6-month adjuvant regimen for patients with colon carcinoma that has no detrimental effect on their quality of life.
Adult↗
Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study.
BACKGROUND: Oxaliplatin is a new cytotoxic agent from the diaminocyclohexane family with proven antitumor activity against colon cancer cell lines. Activity in patients with colorectal carcinoma previously treated with 5-fluorouracil has been studied in three single-agent phase II trials, showing a reproducible response rate of 10%. Here we report a phase II trial with oxaliplatin as a first-line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Twenty-five patients were entered in the study. All of them had metastatic disease without previous chemotherapy, and at least one lesion had to be measurable by computed tomography (CT). Therapy consisted of a two-hour infusion of oxaliplatin at a dose of 130 mg/m2 every 21 days. RESULTS: The overall response rate determined by investigators was 20% (95% CI, 6.8%-40.7%). Eight patients (32%) had stable disease. The median time to disease progression in responders was six months (range four to nine). The median progression-free survival was four months and median overall survival 14.5 months (95% CI, 10-20 months). The main toxic effects were peripheral neuropathy (92%) and laryngopharyngeal dysesthesia (75%). No severe grade 3-4 neurotoxicities (NCI-CTC) were found. Gastrointestinal and hematological toxicities were mild. CONCLUSIONS: Oxaliplatin is an active agent in first-line chemotherapy for advanced colorectal cancer. It was well tolerated, caused no toxic deaths, had low hematotoxicity, well controlled gastrointestinal toxicity, and frequent but mild peripheral neurological symptoms. Therefore, it is of interest to associate oxaliplatin with other active compounds.
Adenocarcinoma↗
Oral idarubicin and cyclophosphamide for metastatic breast cancer in elderly patients.
The authors treated 39 heavily pretreated breast cancer patients, median age 72, with a combined oral regimen featuring idarubicin and cyclophosphamide, administered without hospitalization in cycles repeated every 4 weeks for a total not to exceed idarubicin 400 mg/m2. Treatment was remarkably well tolerated, with generally mild hematological toxicity and only one discontinuation caused by severe neutropenia; non-hematologic toxicity consisted mainly of moderate nausea and vomiting in fewer than half the cycles, and hair loss of various severity in the majority of patients. Therapeutic results were graded as partial responses (13 cases), no change (NC; 11 cases) or progressive disease (11 cases) for a response rate of 37.2% (95% CI: 21.1-53.1%). The authors single out the NC issue as being of special interest, its mere occurrence being rewarding in the circumstance and its duration in excess of 5 months (seen in six cases) almost equivalent to therapeutic success.
Administration, Oral↗
High-versus low-dose levo-leucovorin as a modulator of 5-fluorouracil in advanced colorectal cancer: a 'GISCAD' phase III study. Italian Group for the Study of Digestive Tract Cancer.
BACKGROUND: Although leucovorin (LV) + 5-fluorouracil (5-FU) is considered the treatment of choice for advanced colorectal cancer in most countries, the optimal schedule of this combination has not yet been established. Low-dose LV appears to be as active as high-dose LV in the daily-times-five regimen, but no randomized study of the levorotatory stereoisomer (6S-LV) given at two different dose levels has been published. PATIENTS AND METHODS: Between November 1991 and June 1994, 422 patients (all with measurable disease previously untreated with chemotherapy) were randomized to 6S-LV (100 mg/sqm/i.v.) + 5-FU (370 mg sqm/15 min i.v. infusion), both administered for 5 days every 28 days (arm A), or to 6S-LV (10 mg/sqm/i.v./5-FU (doses as above), also given for 5 days every 28 days (arm B). The primary endpoint of the study was the comparison of response rates (WHO criteria): the secondary endpoint was the assessment of survival and tolerability. No evaluation of the quality of life or the symptomatic effect of treatment was planned. RESULTS: The response rate was 9.3% in arm A (95% CI: 5.4-13.1), with 2 CR and 18 PR, and 10.7% in arm B (95% CI: 6.5-14.9), with 3 CR + 19 PR, without any significant difference (P = 0.78). The median time to progression was eight months in both groups and overall survival was 11 months, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects (mucositis and diarrhoea), which were rarely severe (grade 3-4: 5%-10% of patients) and similar in the two groups. CONCLUSIONS: In this large-scale multicentre trial, the low and high doses of 6S-LV appeared to be equivalent in terms of the biochemical modulation of 5-FU in advanced colorectal cancer although, for several reasons (including the timing and the strict criteria of response evaluation, the high number of patients with unfavourable prognostic factors, the multi-institutional nature of the study, the dose and modality of 5-FU administration), the response rate was lower than that reported in some of the other published studies. Given the considerable difference in economic cost between the two dosages, the use of high-dose 6S-LV in the daily-times-five regimen is not recommended in clinical practice.
Adult↗
A neurophysiological study in children and adolescents with Crigler-Najjar syndrome type I.
We studied the neurophysiological features of five patients (age range: 4-20 years) suffering from Crigler-Najjar syndrome type I (CNsI) by means of multimodal (brainstem, somatosensory, motor) evoked potentials and periodic EEG-polygraphic recordings (follow-up: 3 months-4.5 years). Two patients presented with neurological disturbances, consisting mainly of mental slowing, motor impairment and seizures. Both of them presented an abnormal EEG, characterized by slowing of background activity associated with paroxysmal discharges. Liver transplantation was performed in one of these two patients and was followed by improvement of both the neurological picture and EEG activity. In a third patient, clinically normal, after two years of follow-up, the EEG started to show paroxysmal activity during sleep or when evoked by intermittent photic stimulation. In these three patients, multimodal evoked potentials were unremarkable. The remaining two younger subjects did not show any clinical or EEG abnormality. Our findings suggest that, whereas in newborns and infants evoked potentials have been demonstrated as reliable techniques to monitor bilirubin neurotoxicity, in children and adolescents with CNsI, EEG seems to be more sensitive in evaluating patients for neurological damage and effectiveness of therapeutic strategies adopted.
Adolescent↗
Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer.
PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.
Adult↗
Adjuvant chemotherapy in colorectal cancer with high-dose leucovorin and fluorouracil: impact on disease-free survival and overall survival.
PURPOSE: The rationale for using adjuvant chemotherapy in colorectal cancer is to achieve better disease control and thus reduce the high rates of tumor recurrence and mortality in patients who undergo curative surgery. The current literature, including relevant abstracts, on clinical trials of fluorouracil (5-FU) in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer is reviewed. The intent is not to present new data, but to present the reader with a broad perspective and larger patient experience on which to base well-reasoned treatment decisions. DESIGN: Published clinical trials and abstracts presented at the 1996 American Society of Clinical Oncology (ASCO) meeting that assessed 5-FU in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer were surveyed. End points of interest were disease-free survival (DFS), overall survival, and toxicity. RESULTS: In randomized trials that used high-dose leucovorin at doses that ranged from daily-times-five 200 mg/m2 to weekly 500 mg/m2 in combination with 5-FU, significant improvements in both DFS and overall survival were observed over surgery alone (control). In patients treated with high-dose leucovorin/5-FU, DFS rates ranged from 71% to 77% compared with control (58% to 64%). A similar trend was seen in overall survival, with a range of 75% to 84% compared with control (63% to 77%). Toxicities observed for high-dose leucovorin administered on a weekly or daily-times-five schedule were diarrhea, stomatitis, myelosuppression, and nausea. CONCLUSION: Overall, the results of these randomized trials support the use of high-dose leucovorin/5-FU as adjuvant therapy for colorectal cancer. Longer follow-up studies are needed to compare the benefits of these different regimens in terms of survival and to characterize adverse effects, especially those that may not be immediately evident. Adjuvant therapy with high-dose leucovorin/5-FU is an effective regimen that is well tolerated by many patients with colorectal cancer.
Antidotes↗
Paclitaxel, ifosfamide, and carboplatin for the treatment of stages IIIB and IV non-small cell lung cancer: preliminary results.
We have treated 26 consecutive chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer with an innovative regimen based on a 1-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 125 to 250 mg/m2, ifosfamide 3 g/m2 (with mesna), and carboplatin dosed to an area under the concentration-time curve of 5, every 21 days for a total of six cycles in responding or stabilized patients. Among 22 fully evaluable patients, 14 (64%) achieved a partial remission, six had disease stabilization, and two had disease progression. Hematologic toxicity was remarkably mild; only one patient had grade 3 neutropenia (on day 21). Arthralgias/myalgias (grade 3 in nine patients, grade 4 in one patient) and neurologic toxicity (a cumulative sensory neuropathy of grade 3 or 4 in five patients) were the most common side effects and seem to be dose related. To date, few patients are fully evaluable and survival data are clearly immature. Nevertheless, this regimen seems highly active and quite well tolerated, and deserves further evaluation.
Adult↗
Histopathological grading of response to induction chemotherapy in non-small cell lung cancer: a preliminary study.
Management of locally advanced NSCLC is controversial. Induction chemotherapy followed by surgery has become an accepted approach for Stage III disease. However, the clinical assessment of the efficacy of preoperative treatment is inaccurate. We propose a four-grade histopathological evaluation of the response to chemotherapy based on the analysis of 20 evaluable cases and compared with clinical outcome. Follow-up ranged from 12 to 68 months. Correlation between different grading of necrosis and survival is statistically significant. Based on these preliminary results, we suggest that grading of response is a valid parameter to evaluate standard regimens and novel drug associations in larger trials.
Aged↗
Sequential methotrexate and 5-fluorouracil as second-line chemotherapy for advanced colorectal cancer patients pretreated with 5-fluorouracil and leucovorin: a GISCAD study.
The biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and 6-S leucovorin (LV) seems mainly directed at two different intracellular targets, supporting the hypothesis of possible non-cross resistance between these two methods of 5-FU potentiation. Thirty-one patients, all previously treated with 5-FU and LV for advanced colorectal cancer (ACC), were treated with MTX = 200 mg/m2 iv day 1 and 5-FU 600 mg/m2 day 2 with 6-S LV 10 mg/m2 po q 6 h X 6 starting 24 h after MTX, repeated every 2 weeks. Of 30 evaluable patients, 2 Partial Remissions (PR) were achieved (Response Rate = 6.6%; 95% Confidence Interval 0%-14%). Eight patients had disease stabilization (SD). The overall median survival was 5 months (range 1-11). No WHO grade III-IV toxicities were reported. Despite the good tolerability, this combination of MTX, 5-FU and LV rescue has minimal activity in ACC after the failure of 5FU+LV-based chemotherapy.
Adult↗
Epirubicin, cisplatin, and continuous infusion 5-fluorouracil is an active and safe regimen for patients with advanced gastric cancer. An Italian Group for the Study of Digestive Tract Cancer (GISCAD) report.
BACKGROUND: A Phase II confirmatory multicenter trial was performed to evaluate a combination of epirubicin, cisplatin, and continuous infusion 5-fluorouracil (ECF) in treating patients with advanced gastric cancer. METHODS: Fifty-three patients with locally advanced (n = 7) or metastatic (n = 46) gastric cancer received a dose of epirubicin (50 mg/m2) and cisplatin (60 mg/m2) intravenously every 21 days for eight cycles with 5-fluorouracil (200 mg/m2/day) by intravenous continuous infusion for 21 consecutive weeks, administered through a central line using an external pump. RESULTS: Eight complete responses and 22 partial responses (response rate = 56%, 95% confidence interval +/- 13) were achieved. Twelve patients had stable disease. The median duration of response was 10 months (range, 3-21 months), and the median survival for all the patients was 9+ months (range, 2-28 months). Overall toxicity, which was primarily hematologic, was mild with only three patients requiring hospitalization for neutropenic fever. No death due to toxicity occurred. CONCLUSIONS: This study found that the ECF regimen is substantially active in treating patients with advanced gastric cancer and has a favorable pattern of toxicity. This schedule clearly deserves randomized comparative trials for palliation of metastatic disease and for adjuvant purposes.
Adult↗
A comparison of the antiemetic efficacy and safety of intramuscular and intravenous formulations of granisetron in patients receiving moderately emetogenic chemotherapy.
A total of 120 patients were treated with granisetron either intramuscular (i.m.) or intravenous (i.v.) in a crossover design, over two successive cycles of moderately emetogenic chemotherapy. Of the 117 patients evaluable for efficacy, 74.4% receiving i.m. and 76.9% receiving i.v. treatment experienced a complete response (no vomiting, no more than mild nausea, no need for rescue medication and no study withdrawal in the 24 h following the onset of chemotherapy). Only a small proportion of the patients experienced any vomiting, either during the first 24 h or in the follow-up period of 4-10 days. There were no statistically significant differences in any of the efficacy parameters between the two routes administration of granisetron. Both formulations of granisetron were also equally well tolerated. The main treatment-related adverse effects were headache and constipation (experienced by 13-15% of patients); local reactions to i.m. injection of granisetron were experienced by 2.6% of patients.
Adult↗
Oral etoposide as second-line chemotherapy for colorectal cancer: a GISCAD study. Gruppo Italiano Studio Carcinomi Apparato Digerente.
Twenty-one patients with advanced colorectal cancer, all previously pretreated with a fluoropyrimidine-based regimen, received oral etoposide: 100 mg/die for 21 consecutive days, every three weeks. No objective response was achieved; 6 pts had a short-lasting stabilization of their disease. Toxicity was substantial and mainly represented by myelosuppression and alopecia. Protracted administration of etoposide is inactive as second-line treatment of colorectal cancer.
Administration, Oral↗
5-fluorouracil by protracted subcutaneous infusion. A pilot study.
A feasibility study of 5-fluorouracil (5-FU) delivered by long-term subcutaneous infusion (SCI) was carried out in 10 patients with advanced malignancies refractory to conventional treatment. 5-FU: 200 mg/m2/day was administered by an external infusor (Baxter 5 or 7 Multiday) connected with a 21-gauge needle placed in the thoracic wall. Treatment was continued until progression of disease or toxicity. WHO grade II to III mucositis was experienced by two and one patients, respectively. Grade II diarrhea developed in one patient. Local toxicity was substantial but painless and manageable; skin ulceration was experienced by two patients. A total of 88 weeks of therapy was delivered with a median of 8.8 weeks for each patient (range 2 to 16). Two patients (breast and colorectal cancer) achieved a partial remission; two additional cases showed a > 50% decrease in tumor marker levels. In conclusion, the administration of 5-FU by SCI deserves further evaluation, especially in clinical circumstances in which venous access is limited by thrombosis or technical concerns.
Antimetabolites, Antineoplastic↗
Leuprolide and tamoxifen in the treatment of pancreatic cancer. A phase II study.
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Adenocarcinoma↗
Steroid receptor enhancement by natural interferon-beta in advanced breast cancer.
In the current study we investigated the effect of two different doses of natural interferon-beta (IFN-beta) on steroid hormone receptors in 45 patients with advanced breast cancer. IFN-beta seems to regulate the receptor mechanisms, inducing in cutaneous metastases an increase of oestrogen and progesterone receptors. Moreover, using IFN-beta and tamoxifen as a combined therapy in 23 receptor-positive patients, no negative interference of the two drugs was observed and no relevant side-effects due to the treatment were noticed. The modulation of steroid receptor content by IFN-beta in advanced breast cancer might represent an interesting way to ameliorate the clinical responsiveness to anti-oestrogens.
Aged↗