Retrospective comparison of two different schedules of irinotecan, 5-fluorouracil and folinic acid in previously untreated patients with advanced colorectal carcinoma: a single institution experience.

PURPOSE: To compare efficacy and tolerability of weekly irinotecan combined with 5-fluorouracil (5-FU) bolus and folinic acid (FA) regimen (IFL) versus biweekly irinotecan with infusional 5-FU and FA (FOLFIRI) in patients (pts) with advanced stage colorectal cancer. PATIENTS AND METHODS: Treatments outcome of 86 pts (IFL - 38 pts, FOLFIRI - 48 pts) was evaluated. Chemotherapy regimens were as follows: IFL - intravenous (i.v.) infusion irinotecan 125 mg/m(2) over 90 min and 5-FU 500 mg/m(2) preceded by FA 20 mg/m(2) both given by i.v. bolus injection, all repeated on days 1, 8, 15 and 22 every 6 weeks; FOLFIRI - i.v. irinotecan 180 mg/ m(2) on days 1 and 15 with subsequent FA 200 mg/m(2) administered as a 2-hour infusion and i.v. bolus injection of 400 mg/m(2) 5-FU immediately followed by 22-hour i.v. infusion of 600 mg/m(2) 5-FU on days 1, 2, 15 and 16 every 4 weeks. Treatment continued until disease progression or unacceptable toxicity. RESULTS: A total of 152 (mean - 4) IFL cycles and 328 (mean - 6) FOLFIRI cycles were administered. Average dose intensity was 0.8 and 0.78 respectively. Toxicities were mild and manageable for both regimens evaluated. Overall response rate was 36.8% in IFL arm and 44.7% in FOLFIRI arm. At the median follow-up of 16 months in IFL arm and 14 months in FOPFIRI arm the two year survival was 38% and 45%, the median survival was 18 months and 21.5 months, and the median progression free survival was 6 months and 9.4 months respectively. CONCLUSIONS: In our experience, both IFL and FOLFIRI regimens have acceptable toxicity at a similar level of dose intensity. Compared to IFL, FOLFIRI seems to improve progression-free survival.

Irinotecan combined with bolus 5-fluorouracil and folinic acid for metastatic colorectal cancer: is this really a dangerous treatment?

Rothenberg et al called for caution in the palliative use of irinotecan, 5-fluorouracil (5-FU) bolus and leucovorin (IFL schedule), because of early treatment related deaths in C89803 and N9741 studies. The objective of our multicenter phase II study was to evaluate the efficacy and safety of the combination of 5-FU bolus, folinic acid (FA) and irinotecan as first-line chemotherapy for metastatic colorectal cancer. From December 1999 to June 2002 138 patients (pts) were treated. The chemotherapy regimen was as follows: irinotecan 125 mg/m2 i.v. over 90 min and 5-FU 500 mg/m2 preceded by FA 20 mg/m2, both given by bolus, weekly, for 4 weeks every 6 weeks. Treatment continued until disease progression or unacceptable toxicity. Total number of administered cycles was 404. Average dose intensity was 75%. 47 out of 131 evaluable pts achieved a complete (n = 6) or partial (n = 41) response, leading to an overall response rate (RR) of 36% [95% confidence interval (CI) 24% to 48%], stable disease was registered in 50 (38%). The estimated median time to progression and survival were 6.5 months (95% CI 5.2-9.4) and 16.6 months (95% CI 15.1-19.3) respectively. Two-year survival was 35%. Toxicity was well manageable. In 18 (13.8%) pts the chemotherapy was stopped because of toxicity. Treatment related death was not observed. Close clinical monitoring, early recognition of toxicity, immediate therapeutic intervention are recommended for pts receiving IFL. In our experience this regimen has manageable toxicity and appropriate level of dose intensity and seems to be a good option for first-line therapy in metastatic colorectal cancer.

Retrospective comparison of single-agent chemotherapy with weekly 5-fluorouracil or weekly irinotecan in previously treated patients with metastatic colorectal cancer.

UNLABELLED: This study is a retrospective analysis of response, toxicity and freedom from progression of two single-agent chemotherapy regimens in patients with previously treated metastatic colorectal cancer. Thirty-five patients with histologically confirmed measurable metastatic colorectal cancer received chemotherapy after failure of first-line 5-fluorouracil (5-FU) and leucovorin treatment. The median age was 61 years. Twenty-seven patients had liver metastases, 6 had local recurrence, 1 had retroperitoneal lymph node metastases and 1 had lung metastases. Eighteen patients received weekly 2600 mg/m2 5-FU and 17 patients received weekly 125 mg/m2 irinotecan (CPT-11). Treatment was given until disease progression. Total number of cycles was 202 for 5-FU and 248 for CPT-11. The relative dose intensity was 1.0 for 5-FU and 0.84 for CPT-11. No grade 3-4 toxicity was registered in patients who received 5-FU. Grade 3-4 toxicity rates were as follows in those who received CPT-11: vomiting 1 (5.9%) patient in 1 cycle, diarrhea 3 (17.7%) patients in 3 cycles and neutropenia in 3 (17.7%) patients in 3 cycles. No patients manifested febrile neutropenia. Two patients (11.8%) needed hospital admission because of toxicity: 1 for vomiting and 1 for diarrhea. No objective responses were observed in the 5-FU group of patients. Three patients (17.6%) who received CPT-11, achieved partial response with a median duration of 8 months. Stable disease was registered in 3 (17.6%) and 9 (52.9%) patients in 5-FU and CPT-11 groups respectively (p=0.05). Median time to progression was 3.3 months for patients who received 5-FU and 4.2 months for those treated with CPT-11 (not significant). One-year survival was 22.2% and 54.3% respectively (p=0.05). CONCLUSION: Weekly chemotherapy with CPT-11 is tolerated with acceptable toxicity and leads to a better response rate than weekly high dose 5-FU. It also significantly improves survival but does not prolong freedom from progression.

Primary malignant lymphoma of the prostate--a report of three cases.

We report the clinical, morphological and immunohistochemical findings in 3 cases of primary non-Hodgkins malignant lymphoma of the prostate. After treatment with doxorubicin-based chemotherapy, two patients achieved a complete remission, and 1 died of infective endocarditis three months after diagnosis. Until a consensus has been reached regarding the optimal treatment of prostatic lymphoma, therapy should be determined by the histologic type diagnosed and stage of the lymphoma.

Phase II study of weekly high dose fluorouracil in previously treated patients with metastatic colorectal cancer.

UNLABELLED: The purpose of this study was to evaluate the efficacy, toxicity, and safety of outpatient chemotherapy with weekly high-dose 5-fluorouracil (HD-5FU) in previously treated patients (pts) with metastatic colorectal cancer. Previously treated and failed pts with histologically confirmed, measurable metastatic colorectal cancer, performance status (WHO) 0-2 and adequate bone marrow function were eligible for treatment. Patients received 5FU (2.6 g/m2) as a 24-hour continuous infusion. Treatment was repeated weekly. A total of 202 cycles were given. Eighteen pts were enrolled. No pts achieved objective response. In 6 pts (33%), after 4 weeks of treatments, CEA level decreased 25% or more, and after 8 weekly treatments it rose again. Mild myelosuppression rarely occurred. Grade I nausea and vomiting occurred in 2 pts and Grade I diarrhea occurred in 2 pts. Mucositis was not observed. CONCLUSION: In our experience single agent, weekly, high dose 5-FU is well tolerated, but is ineffective as second-line treatment for metastatic colorectal cancer, and has only a marginal effect on CEA level.

[The reoxygenation of superficial tumors in fast-neutron therapy]. / Reoksigenatsiia poverkhnostno-raspolozhennykh opukholei pri terapii bystrymi neitronami.

The paper is concerned with the data on reoxygenation of superficial tumors in 38 patients exposed to densely and scarcely ionizing radiation. Tumor reoxygenation curves are presented. A tumor regression rate and reoxygenation of a tumor with respect to its original size showed correlation during fast-neutron therapy at 6.3 MeV.

[The reaction of tumors and normal tissues to therapy with fast neutrons from the U-120 cyclotron]. / Reaktion von Tumoren und Normalgeweben bei der Therapie mit schnellen Neutronen am Zyklotron U-120.

In the present information results of clinical studies are represented to show the effectiveness of therapy with 6.3 MeV fast neutrons in 45 patients with superficial tumors in head and neck area. The reaction of tumor and of normal tissue was studied in dependence on different physical and biological factors. Two variants of neutron therapy planning were estimated by means of mathematical models of a factor of time-dose-fractionation for neutron (TDFN) from clinical point of view. Results of changes in oxygen-tension within the tumor are represented in 20 patients with metastases in cervical lymph-nodes during neutron therapy. The obtained data show a correlation of regression and reoxygenation rate of the tumor to its initial volume. The reaction of the tumor in therapy with fast neutrons was studied in dependence on its morphological structure. Complete regression of epidermoid and nonepidermoid cancer types was seen in 42 or 89% of the cases. With corrections for adipose tissue and the extent of dose fraction of fast neutrons the clinical test of the mathematical model of TDFN-factor made discernible that the reaction of normal tissue can be prognosticated quite exactly by means of this model in neutron therapy.

[3 years' experience of radiation therapy with fast neutrons on the V-120 cyclotron]. / Trekhletnii opyt luchevoi terapii bystrymi netronami na tsiklotrone V-120.

The paper discusses the results of treatment of 128 patients with head and neck cancer in whom fast neutrons (Y-120; approximately 6.2 MeV) were used as a single procedure or in combination with surgery. Tumors of different histomorphologic structure displayed unequal sensitivity to fast neutrons. Mean disease-free survival in patients with complete regression of tumor was 24 months following neutron therapy alone, 18.5 months after combined neutron-photon treatment and 5.5 months only in controls. Relapse rates were 20 and 15% in patients with pre- and postoperative neutron treatment, respectively, as compared to 52% in controls.

[Local radiation reactions and injuries in neutron and combined therapy of tumors using the U-120 cyclotron]. / Mestnye luchevye reaktsii i povrezhdeniia pri neitronnoi i sochetannoi terapii opukholei na tsiklotrone U-120.

Early local radiation reactions and radiation damage during fast neutron therapy of head and neck tumors were studied. The frequency of moist epidermitis in a radical course of neutron therapy was 33%, that in combined neutron and photon irradiation was 21%. Mucosal reactions were observed in 30-35% of the patients with tumors of the oral mucosa. The most frequent radiation damage in a long-term period were fibrotic changes of the skin and subcutaneous connective tissue.

[Radiation-induced changes in normal tissues during neutron-photon therapy of recurrent cancer of the root of the tongue]. / Luchevye izmeneniia normal'nykh tkanei pri neitronno-fotonnoi terapii retsidiva raka kornia iazyka.

The paper is concerned with a case of a 2-year follow-up of a patient with recurrent cancer of the root of the tongue treated with fast neutrons on the Y-120 cyclotron. Medical history included a preoperative course of photon therapy at a dose of 40 Gy and operation. The total focal dose of fast neutrons of a repeated irradiation course was 11.2 Gy, that of photons--14 Gy corresponding to a total photon equivalent dose of 50 Gy. The authors provided the evidence of late radiation changes of the skin, temporomandibular articulation, pharynx, and the upper esophagus, and analyzed the causes of development of radiation complications.

[Neutron therapy of head and neck tumors]. / Neitronnaia terapiia opukholei golovy i shei.

The results of therapy of 55 head and neck tumor patients using fast neutrons of the Y-120 cyclotron of the Research Institute of Nuclear Physics, Tomsk Polytechnical Institute, were analyzed. For design of courses of neutron and combined neutron-photon therapy formulas of DMF calculation were used in cases of homogeneous and arrhythmic dose fractionation. The authors presented some data on methods of therapy with fast neutrons, dose fractionation schedules, a focal dose value, and time of treatment. Complete tumor regression was noted in 50-54% of cases using fast neutrons alone or in combination with photon radiation. A high sensitivity to neutron radiation of nonepidermoid carcinomas as compared to epidermoid cancer types was established with relation to tumor morphological structure.

[Preparation of patients with head and neck tumors for neutron teletherapy]. / Podgotovka bol'nykh s opukholiami golovy i shei distantsionnoi neitronnoi terapii.

The authors discuss some problems of preradiation preparation of patients with head and neck tumors for neutron teletherapy on the U-120 cyclotron of the Tomsk Polytechnical Institute in the Siberian Branch of the All-Union Cancer Research Center, AMS USSR. Some methods of the manufacture and employment technique of the fixing and forming devices for the optimization of neutron therapy are described.