Mitomycin C, 5Fluorouracil and Folinic Acid in Combination with Alpha 2b Interferon for Advanced Colorectal Cancer

1993 ◽  
Vol 79 (6) ◽  
pp. 393-396
Author(s):  
Rodolfo Mattioli ◽  
Paola Mezzanti ◽  
Rosa Rita Silva ◽  
Nicola Battelli ◽  
Paola Manocchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Mitomycin C ◽  
Progressive Disease ◽  
Advanced Colorectal Cancer ◽  
Complete Response ◽  
Biochemical Modulation ◽  
Significant Toxicity ◽  
Advanced Colorectal Carcinoma ◽  
Grade 3

Aims and Background This study was conducted to investigate the activity and toxicity of 5fluorouracll + folinic acid + mitomycin C combined with alpha 2b Interferon in advanced colorectal cancer based upon recent studies suggesting a possible biochemical modulation of 5 fluorouracil by interferon. Patients and methods Between June 1990 and April 1991 25 previously untreated patients with advanced colorectal carcinoma were treated with mitomycin C 10 mg/m2 iv bolus on day 1, 5fluorouracil 375 mg/m2 on days 1 to 4 and folinic acid 200 mg/m2 on days 1 to 4 every 4 weeks, combined with alpha 2b interferon 3 million U day continuously. Response Of the 25 patients entered into the study, 20 were evaluable for response as 5 patients withdrew due to toxicity (grade 3-4 thrombocytopenia in 4 cases and fatigue in 1). No complete response was recorded, 6 patients had partial remission (30 %; 95 % confidence interval, 10 % to 50 %), 4 experienced no change and 10 showed progressive disease. The toxicity of this regimen was significant, particularly myelosuppression. Conclusions This combination showed a significant toxicity and low response rate compared with other 5 fluorouracil based regimens in advanced colorectal cancer.

scholarly journals The role of mitomycin C in the treatment of patients with advanced colorectal cancer resistant to 5-fluorouracil-folinic acid chemotherapy

2001 ◽  
Vol 12 (4) ◽  
pp. 575 ◽  
Author(s):  
S.A. Grumett ◽  
V.R. Archer ◽  
R. Midgley ◽  
P. Mulholland ◽  
S. Nicum ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Mitomycin C ◽  
Advanced Colorectal Cancer

Bevacizumab plus FOLFOX7 as first line treatment in patients with advanced colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15092-e15092
Author(s):  
M. Oukkal ◽  
F. Kara ◽  
S. Difi ◽  
D. Bouzidi ◽  
K. Bentabak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Progressive Disease ◽  
Advanced Colorectal Cancer ◽  
Complete Response ◽  
Severe Toxicity ◽  
Vascular Endothelial ◽  
Significant Survival ◽  
Promising Treatment ◽  
Ecog Ps ◽  
Endothelial Growth Factor

e15092 Background: Bevacizumab a monoclonal antibody against vascular endothelial growth factor (VEGF) has shown in combination with chemotherapy a significant survival improvement in pts with advanced colorectal cancer (F. Kabbinavar JCO 2005 and H. Hurwitz NEJM 2004). In this study we investigated the safety and the efficacy of the addition of bevacizumab to FOLFOX7 regimen in pts with metastatic colorectal cancer. Methods: Inclusion criteria: Histological proven colorectal carcinoma, measurable disease at time of inclusion, no prior chemotherapy (adjuvant chemotherapy allowed), no CNS metastasis, no peripheral neuropathy, no other serious concomitant illness, ECOG PS ≤ 2, Urine dipstick of proteinuria <2+, adequate renal and liver function, good bone marrow reserve and informed consent. Pts received bimonthly Oxaliplatin 130 mg/m2 D1, Folinic acid 400 mg/m2 D1, Fluorouracil 2400 mg/m2 46 hours continuous infusion and Bevacizumab 5mg/kg D3 Results: From April 2005 to June 2007, 47 pts (M/F = 28/19, colon/rectum = 28/19) were enrolled in the study. Median age is 52,7 years old (32–74). They received 452 cycles, median=7 range (1–18). All pts were evaluable for toxicity and survival and 46 for responses. Complete response (CR) was achieved in 3 pts (6.6%), partial response (PR) in 28 pts (60.8%), stable disease in 4 pts (8.7%) and progressive disease in 11 pts (24%). The overall response rate (ORR=CR+PR) is 67.3%. Severe toxicity (CTC/NCI ¾ Grade) related to chemotherapy was neuropathy 5.3%, neutropenia 8.4%, anaemia 3.3%, thrombocytopenia 1.8%, vomiting 8.2%, diarrhoea 2.9%, stomatis 4.9% and allergy 0.7%. Toxicity related to Bevacizumab was bleeding CTCNCI grade 1 and 2 in 40.8%, hypertension grade 1 qnd 2 in 3.7% qnd grqde 3 in 0.2. proteinuria grade and 2 in 13.7%. 1 case of phlebitis and 1 case of Bevacizumab allergy Conclusions: Bevacizumab and FOLFOX7 combination is a promising treatment with high efficacy and safety profile for pts with advanced colorectal cancer No significant financial relationships to disclose.

Bevacizumab plus infusional 5-FU, leucovorin and irinotecan (FOLFIRI) for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: A pilot study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14593-14593
Author(s):  
H. Kwon ◽  
D. Lee ◽  
S. Kim ◽  
S. Y. Oh ◽  
H. J. Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Overall Survival ◽  
Advanced Colorectal Cancer ◽  
Bowel Perforation ◽  
Complete Response ◽  
Time To Progression ◽  
Humanized Monoclonal Antibody ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Combination Regimens

14593 Background: The humanized monoclonal antibody bevacizumab inhibits angiogenesis, and improves survival when combined with chemotherapy for advanced colorectal cancer. The purpose of this trial is to evaluate the combination of bevacizumab with infusional 5-FU, leucovorin and irinotecan (FOLFIRI) in patients with advanced colorectal cancer pretreated with combination regimens including 5-fluorouracil (5- FU), leucovorin (LV) and irinotecan or 5-FU, LV and oxaliplatin. Methods: A total 14 patients (median age 56 years) with advanced colorectal cancer, all of them had progressed after oxaliplatin and irinotecan based combination chemotherapy, were enrolled in this study. Patients were treated with 2 hour infusion of irinotecan 150 mg/m2 on day 1, plus bevacizumab 5 mg/kg iv infusion for 90 minute on day 2, intravenous (iv) injection of leucovorin 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 hour continuous infusions of 600 mg/m2 given on 2 consecutive days every 14 days. Results: The median cycles of chemotherapy were six (range 3 to 12). The response rate was 28.5%, one patient (7.1%) had a complete response, and three patients (21.4%) had a partial response. Eight patients (57.1%) had stable disease, and two patients (14.3%) progressed. The median time to progression was 3.9 months (95% confidence interval (CI) 2.0–8.7 months), and the median overall survival was 10.9 months (95% CI 9.6–12.1 months). Grade 3/4 neutropenia occurred in 5 patients, among them 2 patients developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one patient. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events were not occurred in total 90 cycles. Conclusions: Bevacizumab with FOLFIRI is well tolerated and improves survival in heavily treated advanced colorectal cancer patients. Further studies are needed to confirm these results. No significant financial relationships to disclose.

SOLTI NeoPARP: A phase II, randomized study of two schedules of iniparib plus paclitaxel and paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1011-1011 ◽  
Author(s):  
Antonio Llombart ◽  
Ana Lluch ◽  
Cristian Villanueva ◽  
Suzette Delaloge ◽  
Serafin Morales ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Anticancer Agent ◽  
Triple Negative ◽  
Randomized Study ◽  
Complete Response ◽  
Significant Toxicity ◽  
Clinically Significant ◽  
Grade 3 ◽  
Dose Modifications ◽  
To Receive

1011 Background: Iniparib is an anticancer agent with a mechanism of action still under investigation. A phase 2 randomized neoadjuvant study in patients (pts) with TNBC was designed to explore the activity and tolerability of two schedules of iniparib with weekly paclitaxel (PTX). Here we report the efficacy and safety results from a planned interim analysis (IA). Methods: The trial accrued a total of 141 pts in October 2011, of whom, 74 are included in this IA. All were chemo-naive, histologicallyconfirmed Stage II-IIIA TNBC (IIA 47%; IIB 35%; IIIA 16%) with a median age of 50 yr. Triple negative status was centrally confirmed [ER/PR <10%, HER2 IHC (0+, 1+) or FISH negative]. Pts were randomized (1:1:1) to receive weekly PTX (80 mg/m2, IV, d 1; N=25) alone or in combination with iniparib, either on a once weekly (QW) (11.2 mg/kg, IV, d 1; N=25) or twice weekly (BIW) (5.6 mg/kg, IV, d 1, 4; N=24) schedule. The total planned treatment duration was 12 wks. The IA endpoint is pathological complete response in the breast (pCR) as assessed by independent pathologists. Results: Two/2/3 pts in the PTX/QW/BIW arms, respectively, discontinued due to progressive disease per RECIST. Another 3/2/2 pts, respectively, discontinued due to investigator decision or an adverse event (AE). Thirteen pts presented with Grade 3/4 Treatment Emergent AE: 3 pts in PTX arm (1 neutropenia, 1 presyncope, 1 ALT elevation), 3 in QW arm (1 lymphopenia, 1 hyperkalemia, 1 pulmonary embolism), and 8 in the BIW arm (1 febrile neutropenia, 3 neutropenia, 1 aphonia, 1 syncope, 1 radius fracture and 1 vertigo). Laboratory Grade 3/4 neutropenia occurred in 4% of pts in PTX, 0% in QW and 21% of BIW arms, with 1/2/3 pts, respectively, requiring G-CSF usage. There were 4/7/6 pts in the PTX/QW/BIW arms with PTX dose modifications. Four pts (16%) in PTX arm, 4 pts (16%) in the QW arm and 6 pts (25%) in the BIW arm had confirmed pCR in the breast. Conclusions: In this IA population, the addition of iniparib regardless of the schedule to weekly PTX did not seem to add clinically significant toxicity. pCR rate in the breast is similar across treatment arms at this IA. NCT01204125.

Multimodal Biochemical Modulation of 5-Fluorouracil Activity in Advanced Colorectal Cancer with Allopurinol, Folinic Acid and Dipyridamol

1990 ◽  
Vol 2 (2) ◽  
pp. 123-126 ◽  
Author(s):  
N. Tsavaris ◽  
A. Zinelis ◽  
N. Karvounis ◽  
D. Beldecos ◽  
N. Mylonacis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Advanced Colorectal Cancer ◽  
Biochemical Modulation

Mitomycin-C and capecitabine as salvage chemotherapy in pre-treated patients with advanced colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14595-14595 ◽  
Author(s):  
C. G. Gennatas ◽  
V. Michalaki ◽  
S. Gennatas ◽  
J. Kouvaris ◽  
V. Smyrniotis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitomycin C ◽  
Median Overall Survival ◽  
Advanced Colorectal Cancer ◽  
Patient Characteristics ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Female Ratio ◽  
Significant Toxicity ◽  
Male Female Ratio

14595 Background: To assess the activity and tolerability of the combination of Mitomycin C and Capecitabine in patients with metastatic colorectal cancer after failure of irinotecan, 5-fluorouracil (5-FU), folinic acid and oxaliplatin-containing regimens. Methods: We retrospectively reviewed 31 patients with pre-treated advanced colorectal cancer. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1000 mg/m2 twice daily on days 1–14, was initiated. Cycles were repeated every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle. Results: Main patient characteristics were median age 63 years (range, 45–73); male/female ratio, 19/12. One hundred forty- six courses of therapy were given (median number, 3; range, 2–9). All patients were assessable for response, and all were assessable for toxicity. Fourteen patients had stable disease (45%). Median time to progression was 3 months (range, 1–10) and median overall survival was 8 months (range, 3–28). The regimen was very well tolerated without significant toxicity. Grade 2 toxicities were palmar-plantar erythema 6%, hematological 35%. Conclusions: Our findings suggest that the combination of Mitomycin C and Capecitabine in pre-treated patients with advanced colorectal cancer is safe and effective with an acceptable toxicity profile and a convenient administration schedule. However, further evaluation of other salvage regimens seems to be warranted. No significant financial relationships to disclose.

Dose escalating study of 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) and cetuximab in first-line therapy of patients with metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15025-e15025
Author(s):  
T. Trarbach ◽  
K. Schuette ◽  
J. Stoehlmacher ◽  
E. Goekkurt ◽  
H. Guenther ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Complete Response ◽  
First Line Therapy ◽  
Highly Active ◽  
Grade 3

e15025 Background: Highly active chemotherapy schedules are necessary in several clinical situations, i.e. for conversional chemotherapy in order to resect liver metastases. Adding oxaliplatin or cetuximab to 5-FU / FA / irinotecan was shown to increase the efficacy of chemotherapy in patients with metastatic colorectal cancer (Falcone et al, JCO 2007, Van Cutsem et al, ASCO 2008). Methods: We performed a phase I study in patients (pts) with metastatic colorectal cancer, WHO PS 0–1 who had not been pretreated for metastatic disease. They received cetuximab (500 mg/m2, 2h), oxaliplatin (85 mg/m2, 2h), folinic acid (400 mg/m2, 2h), irinotecan (95, 125, or 165 mg/m2, 1h), 5-FU (3200 mg/m2, 46 h), each on day 1 in biweekly cycles. Dose was escalated if dose limiting toxicities (DLT) were absent in the first three pts per cohort, or if <2 DLTs in six pts. Non-evaluable pts were replaced. Pts were not selected for EGFR IHC or KRAS status. Results: Twenty-one pts were enrolled into the study between Jan 2007 and June 2008, six evaluable pts per each cohort. Two pts who had adverse events deemed unrelated to study during the first cycle (morphine overdosing, mechanical ileus) were replaced, one patient (port dysfunction during first dose) was excluded from analysis. Patient characteristics were as follows: median age 59 (33–72) years, 16 pts WHO PS 0, 15 pts male, 10 pts rectal cancer primary, 3 pts previous adjuvant chemotherapy. In the first two cohorts, 95 and 125 mg/m2 irinotecan, one DLT occurred per dose level (neutropenia gr. 4 and diarrhea gr. 3). In the 165 mg/m2 cohort, 2 DLTs were observed (neutropenia grade 4). Most common grade ≥ 3 toxicities were neutropenia (40%), diarrhea (25%), skin toxicities (15%), thrombopenia (10%) and infections (15%). One patient had a confirmed complete response, 14 pts had confirmed partial response (ORR 75%, 95% CI: 51–91%), 5 pts stable disease. Median progression free survival has not yet been reached. Conclusions: With the combination of FOLFOXIRI/cetuximab, the recommended dose of irinotecan is 125 mg/m2 for further investigation in clinical trials in patients with good performance status. The observed response rate of 75% is very promising. [Table: see text]

scholarly journals Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer

2017 ◽  
Vol 18 (9) ◽  
pp. 694-704 ◽  
Author(s):  
Avital Lev ◽  
Safoora Deihimi ◽  
Elena Shagisultanova ◽  
Joanne Xiu ◽  
Amriti R. Lulla ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitomycin C ◽  
Advanced Colorectal Cancer
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