Ivan Popov

What Is the Best Sequence of Chemotherapy in Advanced Colorectal Cancer? Final Results of a Five-Arm Study

One hundred and ninety-three patients were assigned to receive 5-FU/LV, irinotecan and oxaliplatin in five different sequential treatment groups: Mayo Clinic Regimen (MCR) + LV5FU2 (group A); MCR + irinotecan (350 mg/m2) (group B); MCR + FOLFIRI (group C); MCR + FOLFOX4 (group D); FOLFIRI + FOLFOX4 (group E). The results were as follows: group A (32 patients), median overall survival (OS) 14 months, median time to progression (TTP1) 6 months, median TTP2 5 months, response rate (RR1) 22%, RR2 25%; group B (27 patients), OS 11 months, TTP1 6 months, TTP2 3 months, RR1 22%, RR2 19%; group C (43 patients), OS 14 months, TTP1 5 months, TTP2 5 months, RR1 12%, RR2 19%; group D (45 patients), OS 15 months, TTP1 5 months, TTP2 4 months, RR1 18%, RR2 20%; group E (46 patients), OS 19 months, TTP1 9 months, TTP2 5 months, RR1 39%, RR2 25%. There was a significant difference in OS (p < 0.005) between groups E vs. B and A, D vs. B. Sequential therapy with 3 active drugs (FOLFIRI + FOLFOX4) was the most efficacious combination in comparison with any other two drug combinations applied in our study.

Double-Barreled Wet Colostomy: Urinary and Fecal Diversion

PURPOSE Double-barreled wet colostomy represents simultaneous urinary and fecal surgical diversion performed most commonly after pelvic exenteration as a palliative procedure or after actinic damage. We report the structural and functional results of double-barreled wet colostomy with special attention to surgical technique, morbidity and functional results compared to those described in the available literature. MATERIALS AND METHODS We retrospectively followed 38 patients who underwent double-barreled wet colostomy at our institution from April 2003 to November 2007. The parameters were patient age and gender, the indication for double-barreled wet colostomy, postoperative morbidity and mortality, length of hospital stay and functional assessment by excreting excretory urography. RESULTS A total of 38 double-barreled wet colostomies were performed at our institution, including 24 following total pelvic exenteration, 14 without resection, 9 in inoperable tumor cases and 5 in actinic damage cases. The postoperative morbidity rate was 15.7% with no treatment related mortality. Two patients had late postoperative complications, including stenosis of the ureterocolonic anastomosis and conduit necrosis, respectively. CONCLUSIONS In our experience double-barreled wet colostomy has an acceptable morbidity and mortality rate, is performed without technical difficulties and does not require prolonged operative time. Double-barreled wet colostomy represents the procedure of choice in patients who require concurrent urinary and fecal diversion.

Tumor ‘Flare’ Hypercalcemia – An Additional Indication for Bisphosphonates?

The most serious, potentially life-threatening manifestation of ‘flare’ is hypercalcemia, registered in 4–5% of breast cancer patients with bone metastases, usually during the first few weeks of tamoxifen treatment. There are no specific treatment recommendations for flare hypercalcemia, except tamoxifen withdrawal. There are no reports on the use of bisphosphonates in the treatment of flare hypercalcemia. Among 87 hypercalcemic patients with metastatic breast cancer observed during a 7-year period, 10 patients had tamoxifen-induced hypercalcemia. Diagnosis of flare hypercalcemia was based on the normal pretreatment values of serum calcium and the development of hypercalcemia within a maximum of 6 weeks of hormonal drug initiation. The median time from hormonal drug initiation to flare hypercalcemia was 14 days, the median duration 8.5 days, and the median calcium level was 3.09 mmol/l (range 2.79–4.46 mmol/l). All patients were treated with hydration, and 7 patients with calcium levels above 3.0 mmol/l were also treated with disodium pamidronate in various single doses (30–90 mg/24 h). Normocalcemia was achieved in all patients, and tamoxifen was continued without relapse of hypercalcemia. Median survival was 177 days (range 12–570 days). It seems that the use of bisphosphonates in the treatment of flare hypercalcemia could allow safe readministration of tamoxifen and prevent premature and unjustified tamoxifen discontinuation. Flare hypercalcemia might represent one more indication for the use of bisphosphonates.

Vinblastin-carboplatin for metastatic cutaneous melanoma as first-line chemotherapy and in dacarbazine failures

SummaryFirst-line treatments of metastatic melanoma are usually decarbazine (DTIC) and/or α-interferon based, with response rates in the range of at most 20–30%. In this study, initiated, in fact, by a temporary DTIC shortage in the country, we have assessed the efficacy and toxicity of a vinblastine — carboplatin regimen for metastatic melanoma. The regimen was subsquently applied in two cohorts of patients: a chemotherapy-naive one and in DTIC failures (because the regimen was claimed non-cross-resistant). The regimen contained 6 mg/m2 vinblastine on d 1 and 450 mg/m2 carboplatin on d 1 for 3 wk. In the chemotherapy-naïve cohort, 50 patients were included, 29 males and 21 females, median age 54 yr (range: 33–68), performance status 0+1 for 26 patients and 2+3 for 24 patients. Forty-eight patients were evaluable for activity. The response was the following: complete response (CR), 1/48 (2%); partial response (PR), 13/48 (27%); stable disease (SD), 20/48 (42%); progressive disease (PD), 14/48 (29%). The overall response rate was 14/48 (29%). The median response duration was 7 mo (range: 3–14); the median time to progression was 4 mo (range: 2–14). Toxicity included granulocytopenia and thrombocytopenia grade IV in 3/50 patients and nausea grade II in 8/50 patients. In the DTIC-failures cohort, 58 patients were included, 38 males and 20 females, median age 51 yr (range: 20–65), performance status 0+1 for 25 patients and 2+3 for 33 patients. All 58 patients were evaluable for activity. The response was the following: CR 3/58 (5%), PR 4/58 (7%), SD 10/58 (17%), PD 41/58 (71%). The overall response rate was 7/58 (12%). The median response duration was 11 mo (range: 3–24); the median time to progression was 4 mo (range: 2–24). Toxicities included granulocytopenia grade IV in 4/58 patients and nausea grade II in 4/58 patients. Thus, despite the fact that the regimen achieved a response rate comparable to DTIC in a first-line setting, the lack of cross-resistance did not prevent it from being of limited activity in DTIC failures, although, even in this group, several long-lasting responses and stabilizations were noted.

Efficacy and safety of bevacizumab in combination with oxaliplatin, irinotecan and fluoropyrimidine-based therapy in advanced colorectal cancer

Methods: This was a controlled, prospective, multicentre, cohort study. Thirty patients with advanced colorectal cancer were enrolled into this study. Bevacizumab was applied with oxaliplatin-, irinotecan-, 5FU- or capecitabine -based chemotherapy in the first-, second- or third-therapy lines. Totally 261 cycles were applied. The median number of applied cycles per patient was 8 (range 2-16). Results: Objective tumor response (RR) was seen in 11 patients 37% (95%CI 19-69%) calculated on an intention-to-treat basis. The median duration of response was 12 months. Three of 11 patients (27%) with PR had secondary surgery. RR was seen in 9 of 16 patients (56%) who received bevacizumab in the first-line treatment and in 2 of 14 patients (14%) who received therapy in the second+ lines (p=0.02). Clinical benefit (PR+SD) was seen in 22 (74%) patients. 75% of patients achieved clinical benefit in the first-line and 74% in the second+ chemotherapy lines. The median time to progression (TTP) of the patients is was 9 + months (95%CI 7 - + ∞) at the moment of this analysis. The median TTP of patients who received bevacizumab in the first line was 11 months (95%CI 8 - + ∞). The median TTP of patients who received bevacizumab in the second+ lines was 5.5 months (95%CI 4 - + ∞) (p=0.015). The median survival time (OS) for all patients was 9 + months (95%CI 7 - + ∞). The median OS at the moment of analysis was 11 months (95%CI 9 - + ∞) for patients receiving bevaci- zumab in the first line, and 7 months for patients receiving the drug in the second+ lines (95%CI 6 - + ∞) (p=0.024). The incidence of any toxicity grade 3-4 was less than 10%. Bevacizumab associated incidence of grade 3-4 side effects did not exceed 5%. Hypertension 5% and thromboembolism 5% were the most frequent events. Gastrointestinal perforation did not occur. There was one toxic death due to sepsis and not directly associated with bevacizumab toxicity. Conclusion: Bevacizumab can safely be added to different chemotherapeutic regimens in first- and second+ line. The con- ferred benefit in overall survival, TTP and response rate obviously requires randomized trials.

Prognoza bolesnika s potencijalno izlečivim karcinomom kolorektuma

Karcinom kolorektuma predstavlja jednu od najucestalijih malignih bolesti. Da bi procena lekara o trajanju života bolesnika i/ili uspeh lecenja bili sto precizniji, u onkologiji se koriste faktori prognoze i predikcije. Faktore prognoze koristimo za definisanje osnovne prognoze u vreme dijagnosti kovanja neoplazme, koji predviđaju bioloski potvncijal maligne bolesti. Njima se pomažemo u proceni koristi i troskova primene pojedinih programa lecenja. Faktore predikcije koristimo u slucaju kada procenjujemo kvantitativnu ili kvalitativnu razliku u odgovoru za tacno određeno lecenje sto nam omogucava da primenimo ono lecenje koje je najefikasnije. U clanku se prikazuje kako histopatolosko stepenovanje, kao i kvalitet hirurskog lecenja, uticu na trajanje života i ucestalost recidiva bolesti kod osoba obolelih od karcinoma kolorektuma. Napredak u ovim oblastima, kao i napredak u lecenju lekovima, otvara novu perspektivu u onkologiji koja do pre nekoliko godina nije postojala mogucnost izlecenja metastatske bolesti.