Therapie des metastasierten kolorektalen Karzinoms

Treatment of advanced colorectal carcinoma (aCRC) has changed considerably over the past few years and is becoming increasingly individualized. In addition to highly effective chemotherapeutics, monoclonal antibodies became available for treating CRC a few years ago. The decision as to the type and duration of treatment now heavily depends on the extent of the disease and whether the patient is symptomatic. The existence of certain genetic changes also affects the choice of substance. The aim of palliative treatment remains to extend the patient’s life and to improve quality of life. In a patient group with primarily non-resectable liver metastases that may become resectable following a reduction in size, intensive neoadjuvant therapy can create the option of secondary surgical removal of the tumor manifestations and thus potentially cure the patients.     

Neuere Aspekte in der palliativen Behandlung des metastasierten kolorektalen Karzinoms

Background: Despite a decrease in both the incidence of colorectal carcinoma and the mortality due to this disease, it is still the second most common cause of death in the Western world. Refined surgery and adjuvant chemotherapy have not been able to prevent the frequent recurrence of colorectal cancer, often in a nonresectable state. In this palliative situation, which may already occur during initial presentation, the following treatment is indicated: best supportive care and a differential and stepwise chemotherapy. Palliative chemotherapy retards the progression of cancer disease and improves survival (from 6–9 months to 15–18 months). Chemotherapy should already be started in asymptomatic patients, if cancer disease is progressive. Chemotherapy: 5-Fluorouracil (5-FU) remains the key drug for palliative chemotherapy. Drug effects and side effects critically depend on the mode of application and on biomodulation (e. g. by folinic acid [leucovorin, LV]). Compared with the traditional bolus therapy of 5-FU/LV, we prefer infusional therapy for 24 hours because of its higher effectivity and fewer side effects. Further drugs that may be given in addition to or as an alternative to 5-FU, are sodium folinate, raltitrexed and oral fluoropyrimides (so-called prodrugs, e. g., capecitabine and tegafur-uracil [UFT]). These drugs are still under clinical investigation. Capecitabine, in particular, appears to be a useful alternative for intravenous 5-FU therapy. When compared with the traditional 5-FU bolus therapy (Mayo regimen), capecitabine is at least equally effective, but has fewer side effects. Furthermore, it can be given orally. If treatment failure occurs under 5-FU, the application of oxaliplatin or irinotecan may be useful for second- and third-line therapy (partial remission rates of 10% or 13–15%). First-Line Therapy: Four randomized phase-III studies demonstrate the effectiveness of additional therapy with oxaliplatin and irinotecan in combination with 5-FU for first-line chemotherapy of colorectal cancer. Triple therapy improves remission rates, quality of life and (shown only for irinotecan/5-FU/LV) survival rate, but causes more side effects and costs.     

Neuere Aspekte in der palliativen Behandlung des metastasierten kolorektalen Karzinoms

Zusammenfassung Hintergrund: Das kolorektale Karzinom stellt trotz einer Abnahme von Inzidenz und Todesrate die zweithäufigste tumorbedingte Todesursache in der westlichen Welt dar. Ungeachtet der Erfolge operativer Verfahren (Stichwort Tumorchirurgie) und der adjuvanten Therapie entwickeln sich insbesondere bei lokal fortgeschrittenen Primärtumoren häufig Rezidive und Metastasen, die eine kurative Behandlung nicht mehr erlauben. In dieser palliativen Situation, die häufig auch schon bei der initialen Präsentation besteht, ist neben einer bestmöglichen supportiven Therapie eine differenzierte und abgestufte Chemotherapie angeraten. Eine palliative Chemotherapie verzögert die Krankheitsprogression und verbessert Lebensqualität und Überleben (von 6-9 Monaten auf 15-18 Monate). Mit einer Chemotherapie sollte bereits im asymptomatischen Stadium bei nachweisbarem Krankheitsprogress begonnen werden. Chemotherapie: Eckpfeiler der palliativen Chemotherapie ist weiterhin das 5-Fluorouracil (5-FU). Die Wirkungen und die Nebenwirkungen sind entscheidend abhängig von der Darreichungsform und der Biomodulation (z. B. durch Calciumfolinat in Form von Leucovorin [LV]). Hervorzuheben ist besonders die 24-stündige Infusionsbehandlung mit 5-FU/LV, die wir gegenüber der traditionellen Bolustherapie aus Gründen der höheren Effektivität bei weniger Nebenwirkungen in der Primärtherapie des kolorektalen Karzinoms bevorzugen. Weitere Substanzen, die additiv bzw. alternativ zum 5-FU eingesetzt werden können, umfassen Natriumfolinat, Raltitrexed, und orale Fluoropyrimidinanaloga (sog. Prodrugs) wie Capecitabine und Tegafur-Uracil (UFT). Diese Pharmaka sind z. Z. noch in der klinischen Erprobung. Insbesondere das Capecitabine ist dem traditionellen 5-FU-Bolusschema (Mayo-Schema) bei weniger Nebenwirkungen mindestens ebenbürtig. Es hat zudem den Vorteil, dass es oral gegeben werden kann. Bei Versagen einer 5-FU-Behandlung kommen in der Zweit- und Drittlinientherapie Oxaliplatin bzw. Irinotecan mit einer Ansprechrate (i. S. einer partiellen Remission) von 10 bzw. 13-15% zum Einsatz. Erstlinientherapie: Vier randomisierte Phase-III-Studien des Jahres 2000 belegen den Nutzen einer additiven Gabe von Oxaliplatin und Irinotecan zuzüglich zu 5-FU/LV auch in der Primärtherapie des kolorektalen Karzinoms. Sie zeigen übereinstimmend eine höhere Ansprechrate und eine verbesserte Lebensqualität unter der Tripeltherapie und unter Therapie mit Irinotecan/5-FU/LV sogar eine verbesserte Überlebensrate. Diesem Erfolg stehen eine höhere Nebenwirkungsrate und ein höherer Therapiepreis gegenüber. Abstract Background: Despite a decrease in both the incidence of colorectal carcinoma and the mortality due to this disease, it is still the second most common cause of death in the Western world. Refined surgery and adjuvant chemotherapy have not been able to prevent the frequent recurrence of colorectal cancer, often in a nonresectable state. In this palliative situation, which may already occur during initial presentation, the following treatment is indicated: best supportive care and a differential and stepwise chemotherapy. Palliative chemotherapy retards the progression of cancer disease and improves survival (from 6-9 months to 15-18 months). Chemotherapy should already be started in asymptomatic patients, if cancer disease is progressive. Chemotherapy: 5-Fluorouracil (5-FU) remains the key drug for palliative chemotherapy. Drug effects and side effects critically depend on the mode of application and on biomodulation (e. g. by folinic acid [leucovorin, LV]). Compared with the traditional bolus therapy of 5-FU/LV, we prefer infusional therapy for 24 hours because of its higher effectivity and fewer side effects. Further drugs that may be given in addition to or as an alternative to 5-FU, are sodium folinate, raltitrexed and oral fluoropyrimides (so-called prodrugs, e. g., capecitabine and tegafur-uracil [UFT]). These drugs are still under clinical investigation. Capecitabine, in particular, appears to be a useful alternative for intravenous 5-FU therapy. When compared with the traditional 5-FU bolus therapy (Mayo regimen), capecitabine is at least equally effective, but has fewer side effects. Furthermore, it can be given orally. If treatment failure occurs under 5-FU, the application of oxaliplatin or irinotecan may be useful for second- and third-line therapy (partial remission rates of 10% or 13-15%). First-Line Therapy: Four randomized phase-III studies demonstrate the effectiveness of additional therapy with oxaliplatin and irinotecan in combination with 5-FU for first-line chemotherapy of colorectal cancer. Triple therapy improves remission rates, quality of life and (shown only for irinotecan/5-FU/LV) survival rate, but causes more side effects and costs.     

Vorsorge des kolorektalen Karzinoms

Colorectal cancer is one of the leading causes of cancer-associated morbidity and mortality worldwide. The main risk factors include lifestyle factors, advanced age, positive family history, and male sex. Screening can reduce incidence and mortality of colorectal cancer. In contrast to endoscopy and stool tests which detect occult blood molecular stool tests, virtual endoscopy and capsule endoscopy are so far not established for early detection.     

Screening des kolorektalen Karzinoms

Colorectal cancer is common and suitable for screening. There is general agreement that screening for colorectal cancer in the asymptomatic population without familial risk should begin at age 50. The different screening methods can be separated into methods that mainly detect cancers (fecal occult blood tests, genetic stool tests, blood tests, and the M2-PK test) and methods that diagnose cancers and polyps (colonoscopy, sigmoidoscopy, CT/MRI colonography, and colon capsule endoscopy). Endoscopic methods enable detection and treatment of preneoplastic adenomas and, thus, make cancer prevention possible. In the current German S3 guideline, colonoscopy is recommended as the preferred screening test. For people unwilling to undergo endoscopic screening, the fecal occult blood test is an alternative. Colonoscopy has been part of the German Cancer Screening Program since 2002.     

Multimodale Therapie des kolorektalen Karzinoms

Adjuvant chemotherapy for resected stage III colon cancer is indicated for all patients, including elderly patients >70 years. In general, adjuvant oxaliplatin-fluoropyrimidine chemotherapy should be started within 6 weeks after tumor resection and should be given for a period of 6 months. However, patients aged >70 should receive fluoropyrimidine mono-chemotherapy. This mono-therapy, but not an oxaliplatin-based combination, can also be considered for patients with standard risk stage II tumors without microsatellite instability. In stage II patients with a high risk constellation adjuvant oxaliplatin-fluoropyrimidine combination therapy should be considered. Patients with stage II and III rectal cancer require neoadjuvant radiochemotherapy with fluoropyrimidine followed by adjuvant fluoropyrimidine treatment. There is no role for the use of VEGF- or EGFR-antibodies in the adjuvant therapy of colon cancer or in neoadjuvant therapy of rectal cancer. The prognosis of patients with primary resectable colorectal liver metastases may be improved by adjuvant or perioperative chemotherapy, while neoadjuvant systemic chemotherapy frequently facilitates potential curative resection of initially non-resectable liver metastases.     

Palliative Therapie des kolorektalen Karzinoms

Background

Colorectal cancer (CRC) is the third leading cause of cancer deaths worldwide. Every second patient dies of the disease. The introduction of new and effective chemotherapeutic substances and biologics during the past decade has significantly improved the systemic treatment of patients with metastatic CRC (mCRC). The introduction of the mutational status of the RAS oncogene as the first predictive marker into clinical care is an important step towards the personalization of the treatment in mCRC. The further increasing understanding of genetic dysregulations and signaling networks in metastatic colon cancer leads to modern therapy strategies. The development of novel targeted drugs enables us to selectively disrupt essential signaling networks of tumors.

Conclusion

The understanding of established and new treatment options for mCRC are increasing. Like in non-small cell lung cancer the trend in mCRC treatment moves to new treatment options for molecular subgroups (e.?g. for BRAF mutant, HER2 amplified/overexpressed or mismatch repair deficient tumors) that achieve very good treatment results.

     

Früherkennung des kolorektalen Karzinoms

Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. Colorectal cancer commonly develops slowly via adenomatous polyps, a process usually requiring ≥?10 years. This allows for early detection. Endoscopic polypectomy and surgery of early disease can reduce the incidence and mortality of colorectal cancer. Both hemoccult testing and colonoscopy are the most widely used tests for colorectal cancer screening; however, colonoscopy has the highest sensitivity for colorectal neoplasia. Sigmoidoscopy is not commonly used for screening in Germany. Colon contrast enema is no longer recommended for screening. As colonoscopy serves as a diagnostic and therapeutic tool and is the reference method in hemoccult and sigmoidoscopy studies, it is viewed as the gold standard for the diagnosis of colonic disease. New methods including capsule colonoscopy and virtual colonoscopy have great potential but are currently not recommended for early detection of colonic neoplasia.     

Chirurgische Therapie des kolorektalen Karzinoms im Alter

Colorectal carcinoma is one of the most frequent tumor entities worldwide. The treatment of elderly and mostly polymorbid patients is an outstanding challenge in view of the demographic change with a continuously aging community. Due to the demographic changes the numbers of elderly (>65 years) and very old (≥80 years) patients are steadily increasing in surgical cohorts. This has resulted in higher morbidity and mortality rates in comparison to younger patients, with increased wound healing and cardiovascular complications but with comparable numbers of anastomotic insufficiency. Multivariate analysis revealed age ≥80 years, higher ASA status and emergency operations as independent risk factors for increased in-hospital mortality. With respect to the localization of colorectal cancer a shift to the right has been observed with increasing patient age. Whether minimally invasive surgical techniques can reduce postoperative morbidity and mortality rates in elderly patients requires further evaluation. Nevertheless, a reduction of both was reported without compromising the oncological result. Elderly patients require individualized treatment modalities, which take the extent of comorbidities and personal environment into consideration. So far, the cohort of octogenarians has not been adequately considered in current guidelines; therefore, geriatric expertise is recommended to be able to make a better assessment of benefit-risk ratios, as age itself has no impact on the decision for therapy.