Adjuvant Treatment of Colon and Rectal Cancer: Impact of Chemotherapy, Radiotherapy, and Immunotherapy on Routine Postsurgical Patient Management

Link, K. H.; Staib, Ludger; Kreuser, Ernst-Dietrich; Beger, H. G.

doi:10.1007/978-3-642-80035-1_19

Cited by 27 publications

(39 citation statements)

References 105 publications

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“…The good correlation between cancer incidence rates for both the sites observed in different ethnic populations (1,2) and the shared similar etiology, type of precancerous lesions as well as mode of spread, all give evidence in favor of the first assumption (2). However, differences exist between colon and rectal carcinomas with respect to age and gender of the patient as well as tumor progression and adjuvant treatments (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Different Genetic Features Associated with Colon and Rectal Carcinogenesis

Frattini

Balestra

Suardi

et al. 2004

Clinical Cancer Research

195

127

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Purpose: The issue of whether colon and rectal cancer should be considered as a single entity or two distinct entities is still debated, and there is a need to improve studies addressing the heterogeneity of the pathogenetic pathway leading to sporadic colorectal cancers (SCRCs) as well as to identify biological and/or molecular differences between colon and rectal cancers.Experimental Design: Specimens of SCRCs were analyzed for somatic mutations in APC, K-ras, and TP53 genes and loss-of-heterozygosity of chromosome 18.Results: Eleven SCRCs showed microsatellite instability. APC mutation frequency was significantly lower in microsatellite instability (MIN؉) than in MIN؊ SCRCs. All MIN؊ SCRCs showed ␤-catenin overexpression. A combined analysis of the biomarkers revealed two pathways mainly represented by MIN؊ SCRCs and differently followed on the basis of tumor location, APC-K-ras-TP53-Ch18q and APC-TP53-Ch18q.Conclusions: The APC-␤-catenin pathway is inactivated in MIN؊ SCRCs and represents the first hit of SCRC development. Two preferential pathways followed by SCRCs occur, one K-ras dependent, in agreement with the Fearon and Vogelstein model, and the other K-ras independent. Significant differences between colon and rectal tumors occur in our series of MIN؊ SCRCs. The different pathways observed and their distribution can be summarized as follows: (a) K-ras mutations were more commonly detected in colon than in rectum; (b) the number of mutations detected was significantly higher in colon than in rectal tumors; and (c) a mutational pattern restricted to the APC gene was more common in rectal than in colon tumors. This molecular characterization can be translated into a clinical setting to improve diagnosis and to direct a rationale pharmacological treatment.

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Section: Introductionmentioning

confidence: 99%

Different Genetic Features Associated with Colon and Rectal Carcinogenesis

Frattini

Balestra

Suardi

et al. 2004

Clinical Cancer Research

195

127

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“…In FOGT2, radiotherapy (50.4 Gy) was added to the chemoimmunotherapy arms. The rationales of these trials have extensively been discussed elsewhere [4], Briefly, the baseline treatment (arm A) was chosen and administered according to the Intergroup protocol that had proven the efficacy of 5FU + LEV in adjuvant therapy after resection of stage III colon carcinoma [5,6], We decided to include T4N0M0 colon cancer patients since their prognosis may be comparable to that of UICC III patients [7]. Rectal cancer patients were treated according to the same systemic treatment principles since we, like others [8], share the opinion that not only macrometastases -as usually practiced but also potential micrometastases of colon and rectal cancers should receive the same systemic therapy -but within separate studies.…”

Section: Discussionmentioning

confidence: 99%

“…Any toxic events > W H03 were recorded, W H 04 events were reported to the German 'Bundesinstitut für Arzneimittel und Medi zinprodukte'. The FOGT1 and FOGT2 protocols whose rationales have been outlined in a recent review [4] were accepted by the University Ethics Review Committee of Ulm and in other participating centers. The recent status of toxicity and patient's acceptance is analyzed and dis cussed on study meetings every 6 months with delegates of the partici pating hospitals.…”

Section: Methodsmentioning

confidence: 99%

Acceptance and Toxicity of Postoperative Adjuvant Therapy in Colon and Rectal Cancers

Link¹,

Staib²,

Bernhart³

et al. 1997

Oncol Res Treat

Self Cite

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Purpose: FOGT has initiated two prospective controlled randomized trials to improve adjuvant therapy of colon cancer stages UICC II / T4N0M0 and III (FOGT1) and rectal cancer stages UICC II and III (FOGT2). This interim report analyzes the toxicity and acceptance of the 3 treatment arms. Patients and Methods: ‘Standard group’ (arm A) is treated with 5-fluorouracil (5FU) plus levamisole (LEV, Ergamisol®). In arm B 5FU is modulated by folinic acid (FA, Rescuvolin®) (5FU + FA + LEV), in arm C by interferon alpha (IFNα, Roferon®) (5FU +IFNα + LEV). Rectal cancers, in addition, are irradiated with 50.4 Gy. Chemotherapy doses are adjusted to toxicity if toxic events > WH02 occur. Until October 1996, 56 hospitals recruited a total of 946 patients (FOGT1 521, FOGT2 425 patients). Toxicity and discontinuance rates were noted. Results: Among the 839 patients evaluable according to ‘intention to treat’ (FOGT1: 464, FOGT2: 375 patients), a toxic event > WH02 occurred in 139 patients (17%). Toxicities > WH02 in arms A, B, and C of FOGT1 were 5, 7, and 21%, respectively, whereas the respective values in FOGT2 were 20, 16, and 38%. Discontinuance rates in arms A, B, and C of FOGT1 were 23, 17, and 25%, respectively, while the respective rates in FOGT2 were found to be 20, 20, and 23%. Treatment was stopped in arms A, B, and C of FOGT1 either because of toxicity or on patient’s demand in 11, 8, and 16%. In FOGT2, treatment in arms A, B, and C was terminated for these reasons in 7, 13, and 10% of the cases, respectively. The overall discontinuance rate due to toxicity or patient’s demand was 11%. Toxicity in arm C seemed to be higher than in the other treatment arms and was mainly due to leukopenia and diarrhea. One toxic death was noted in FOGT1 arm A, probably due to 5FU cardiac side effects. Conclusion: The rate of discontinuance is within those of other trials, e.g. the Inter-group Studies (Moertel 1990), so that FOGT1 and FOGT2 trials are safe and acceptable concerning toxicity and patient compatibility.

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“…Voraussetzung für den stadiengerechten Einsatz adjuvanter Chemotherapien beim Kolonkarzinom ist in erster Linie eine genaue Beurteilung der Lymphknotenmetastasierung, da im positiven Fall eine adjuvante Chemotherapie indiziert ist [5][6][7]. Selbst in frühen Tumorstadien wie den auf die Submukosa beschränkten T1-Karzinomen lassen sich bereits bei bis zu 20% aller Patienten Lymphknotenmetastasen nachweisen [8][9][10][11][12][13].…”

Section: Colon: Pro Surgeryunclassified

“…Further cancer infiltration into the submucosa (middle third (sm2) or lower third (sm3), >1,000 μm absolute depth of infiltration) is associated with an increasing risk of lymph node metastasis and should always be treated by surgical resection. [5,6].…”

Section: Colon: Pro Surgerymentioning

confidence: 99%

Kolon: Pro Chirurgie

Weber¹,

Link²

2009

Viszeralmedizin

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Bei Patienten mit T1-Kolonkarzinomen wird die Prognose und Therapie, insbesondere die Indikation zur adjuvanten Chemotherapie, entscheidend vom Status der Lymphknotenmetastasierung beeinflusst. Daher gilt es, anhand von histopathologischen Parametern diejenigen Patienten zu selektionieren, die ein potentiell geringes Risiko für eine Lymphknotenmetastasierung haben und bei guter Prognose endoskopisch behandelt werden können, sowie diejenigen mit einem hohen Risiko, bei denen die Notwendigkeit zur chirurgischen Resektion besteht. Patienten mit einem endoskopisch abgetragenen ‘Low risk’-T1-Karzinom (G1/G2, keine Lymphgefäßinvasion, R0) haben ein geringes Risiko einer Lymphknotenmetastasierung und benötigen lediglich endoskopische Nachuntersuchungen nach 6 Monaten und 2 Jahren. Dagegen finden sich bei Patienten mit einem ‘High risk’-T1-Karzinom (G3/G4, Lymphgefäßinvasion, R1) in bis zu 14,4% Lymphknotenmetastasen, so dass hier immer die chirurgische Resektion indiziert ist. Bei Infiltration des Karzinoms in das obere Drittel der Submukosa (sm1) oder einer absoluten Submukosainfiltration von weniger als 1000 μm sind keine Lymphknotenmetastasen zu erwarten, und die endoskopische Abtragung ist ausreichend. Eine darüber hinausgehende Karzinominfiltration in die Submukosa (mittleres Drittel (sm2), unteres Drittel (sm3), >1000 μm absolute Submukosainfiltration) ist mit einem deutlich ansteigenden Risiko für Lymphknotenmetastasen verbunden, so dass hier die chirurgische Resektion, wenn möglich, immer durchgeführt werden sollte.

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Adjuvant Treatment of Colon and Rectal Cancer: Impact of Chemotherapy, Radiotherapy, and Immunotherapy on Routine Postsurgical Patient Management

Cited by 27 publications

References 105 publications

Different Genetic Features Associated with Colon and Rectal Carcinogenesis

Different Genetic Features Associated with Colon and Rectal Carcinogenesis

Acceptance and Toxicity of Postoperative Adjuvant Therapy in Colon and Rectal Cancers

Kolon: Pro Chirurgie

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