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Adjuvant therapy after neoadjuvant therapy for rectal cancer

Adjuvant therapy after neoadjuvant therapy for rectal cancer
Literature review current through: Jan 2024.
This topic last updated: Jul 06, 2023.

INTRODUCTION — Surgical resection is the cornerstone of curative treatment for rectal adenocarcinomas, but surgery alone provides a high cure rate only for patients with early stage (stage I (table 1)) disease. Many randomized trials have attempted to improve results through the addition of chemotherapy and radiation therapy (RT), both before and after surgery. RT has emerged as an important component of therapy for rectal cancer because of the higher rate of local failure following resection as compared with colon cancer. For patients treated initially with resection, a four-month course of adjuvant chemotherapy is typically added to postoperative chemoradiotherapy (to total six months of adjuvant therapy), and the available evidence is that this is associated with a significant survival benefit [1]. (See "Adjuvant therapy for resected rectal adenocarcinoma in patients not receiving neoadjuvant therapy", section on 'Contribution of adjuvant chemotherapy'.)

More recently, focus has shifted to preoperative (neoadjuvant) application of fluoropyrimidine-containing chemoradiotherapy or short-course "Swedish-style" RT alone, which is now a preferred approach at many institutions for patients with nonbulky transmural (T3/4) (table 1) or node-positive tumors and for those with a positive or threatened mesorectal resection margin. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Indications for neoadjuvant treatment'.)

Many patients who undergo neoadjuvant chemoradiotherapy or short-course RT are offered a four-month period of systemic chemotherapy, which is typically administered after resection. However, practice is variable because there is a paucity of direct evidence to support the administration of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery [2]. Nevertheless, at least in the United States, most oncologists recommend adjuvant chemotherapy in this setting, and the majority of patients receive it [3]. Furthermore, the optimal regimen (ie, an oxaliplatin-containing regimen versus a fluoropyrimidine alone) is debated, particularly in patients who had a complete pathologic response to neoadjuvant therapy.

Postoperative (adjuvant) therapy for resected rectal adenocarcinoma in patients who received neoadjuvant chemoradiotherapy or short-course RT will be reviewed here. Neoadjuvant treatment approaches for rectal adenocarcinoma, the role of adjuvant chemotherapy in patients who have not received neoadjuvant therapy, the preoperative staging evaluation for rectal cancer, the surgical management of rectal adenocarcinoma, treatment of locally advanced unresectable or locally recurrent disease, management of rectal squamous cell cancers (which are treated similarly to anal cancers, with definitive chemoradiotherapy), and posttreatment follow-up are discussed separately:

(See "Neoadjuvant therapy for rectal adenocarcinoma".)

(See "Adjuvant therapy for resected rectal adenocarcinoma in patients not receiving neoadjuvant therapy".)

(See "Clinical presentation, diagnosis, and staging of colorectal cancer".)

(See "Pretreatment local staging evaluation for rectal cancer".)

(See "Radical resection of rectal cancer".)

(See "Surgical treatment of rectal cancer".)

(See "Treatment of locally recurrent rectal adenocarcinoma".)

(See "Treatment of anal cancer", section on 'Rectal squamous cell cancers'.)

(See "Post-treatment surveillance after colorectal cancer treatment".)

BENEFIT OF POSTOPERATIVE CHEMOTHERAPY

Following neoadjuvant short-course RT or long-course chemoradiotherapy — Following resection, we suggest that all patients who underwent neoadjuvant chemoradiotherapy or short-course radiation therapy (RT) alone for locally advanced (T3/4 or node-positive (table 1)) nonmetastatic rectal cancer receive four months of adjuvant chemotherapy, regardless of the pathologic findings at the time of resection.

This recommendation is in keeping with consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) [4]. However, practice is variable, and at some institutions, patients who had a pathologic complete response to neoadjuvant chemoradiotherapy are not routinely offered postoperative chemotherapy, given their overall favorable outcomes.

The evidence used to support adjuvant chemotherapy following neoadjuvant short-course RT or chemoradiotherapy and resection is mainly an extrapolation of the proven benefit of postoperative adjuvant therapy with RT and chemotherapy, which was the standard of care in the era before preoperative combined modality therapy. As an example, a Cochrane review of adjuvant chemotherapy in resectable rectal cancer concluded that fluorouracil-based chemotherapy significantly reduced the risk of death (hazard ratio [HR] 0.83, 95% CI 0.76-0.91) and disease recurrence (HR 0.75, 95% CI 0.68-0.83) [1]. However, in only 1 of the 20 included randomized trials was preoperative chemoradiotherapy administered to all patients [5]. (See "Adjuvant therapy for resected rectal adenocarcinoma in patients not receiving neoadjuvant therapy".)

The benefit of postoperative chemotherapy following preoperative chemoradiotherapy for rectal cancer has been directly addressed in four randomized phase III trials, all of which are flawed, and a meta-analysis of all four trials. In our view and that of others, the available data from these four trials are insufficient to conclude that there is no benefit for postoperative chemotherapy in this setting [6]. In addition, data on the benefit of an oxaliplatin-containing chemotherapy regimen are also available from the randomized phase II ADORE trial.

Phase III Trials

In the European Organisation for Research and Treatment of Cancer (EORTC) trial 22921, patients who had received preoperative RT with or without chemotherapy underwent a second randomization to four cycles of postoperative bolus fluorouracil plus leucovorin or to no further therapy [5]. The addition of chemotherapy, either before or after surgery, significantly improved local control. However, in the latest update, there was no evidence that adjuvant chemotherapy improved 10-year overall survival (51.8 versus 48.4 percent, HR 0.91, 95% CI 0.77-1.09) or disease-free survival (47 versus 43.7 percent, HR 0.91, 95% CI 0.77-1.08) [7]. The rate of adherence to postoperative chemotherapy was 43 percent, indicating that the evaluation of the efficacy of postoperative chemotherapy was inadequate due to failure to adhere to the protocol as written.

An unplanned subgroup analysis limited to the 785 patients who underwent complete (R0) resection and who had no evidence of metastatic disease at surgery (ie, node negative) revealed that the addition of postoperative chemotherapy significantly improved overall survival in those whose tumors were downstaged to postresection pathologic (yp) stage T0-2 disease but not stage ypT3-4 disease [8]. However, the interaction between the tumor downstaging effect of preoperative therapy and the benefit of adjuvant chemotherapy disappeared at later follow-up of this study [7].

A prospective, randomized, cooperative Italian study reported results of 655 patients treated postoperatively with six cycles of bolus leucovorin-modulated fluorouracil compared with observation alone after preoperative chemoradiotherapy [9]. There was no advantage for postoperative adjuvant chemotherapy, either in terms of recurrence rate or overall survival (at five years, 69 versus 70 percent, respectively, with and without adjuvant chemotherapy). Even when the analysis was restricted to patients who had persistent node-positive disease at the time of surgery (ie, ypN+), overall survival rates were not substantially better with adjuvant chemotherapy (five-year overall survival 52 versus 51 percent). Notably, 28 percent of the patients randomized to adjuvant chemotherapy never received it; thus, the evaluation of the efficacy of postoperative chemotherapy was inadequate due to failure to adhere to the protocol as written.

The Dutch colorectal PROCTOR/SCRIPT trials were multicenter prospective trials in which patients with stage II or III rectal cancer who underwent short-course RT or chemotherapy followed by total mesorectal excision were randomly assigned to observation versus postoperative fluorouracil/leucovorin (PROCTOR, n = 177), or observation versus postoperative capecitabine (SCRIPT, n = 292) [10]. Unfortunately, the trials did not reach their full accrual. In a combined analysis of both trials, at a median follow-up of five years, overall survival was not significantly different between groups that did and did not receive adjuvant chemotherapy (five-year overall survival 80 percent with chemotherapy and 79 percent with observation).

In a later analysis, the persistence of perineural invasion, extramural vascular invasion, and tumor budding in the surgical specimen were all associated with significantly worse overall survival, but no factor, either alone or in combination, predicted a beneficial effect of adjuvant chemotherapy [11].

The United Kingdom phase III Chronicle trial compared 18 weeks of postoperative capecitabine/oxaliplatin with no adjuvant treatment in patients undergoing surgery after neoadjuvant fluoropyrimidine-based chemoradiotherapy; unfortunately, the study was closed prematurely due to poor accrual, enrolling only 113 of the estimated 800 patients needed to demonstrate an absolute improvement in disease-free survival from 40 to 50 percent [12]. Three-year disease-free survival was higher in the group randomized to capecitabine/oxaliplatin, but the difference did not reach statistical significance (78 versus 71 percent, HR 0.80, 95% CI 0.38-1.69). Overall survival was similar in both groups. Because of the compromised sample size, the evaluation of the efficacy of postoperative chemotherapy was not definitive.

Meta-analysis – A meta-analysis of individual patient data from all four of these trials concluded that fluorouracil-based chemotherapy did not improve overall survival (HR 0.97, 95% CI 0.81-1.17), disease-free survival (HR 0.91, 95% CI 0.77-1.07), or distant recurrences [13]. However, inexplicably, in subgroup analysis, patients with a tumor 10 to 15 cm above the anal verge had significantly better disease-free survival with adjuvant chemotherapy (HR 0.59, 95% CI 0.40-0.85) and fewer distant recurrences (HR 0.61, 95% CI 0.40-0.94).

The ADORE trial – Direct evidence for the benefit of an oxaliplatin-containing adjuvant regimen in patients with resected rectal cancer after neoadjuvant chemoradiotherapy was provided by the randomized phase II ADORE trial in which 321 patients with curatively resected rectal cancer after neoadjuvant fluoropyrimidine-based chemoradiotherapy and yp stage II (ypT3-4N0) or III (ypT0-4N1-2) disease were randomly assigned to four months of monthly bolus fluorouracil/leucovorin (fluorouracil 380 mg/m2 plus leucovorin 20 mg/m2 daily on days 1 to 5 every 28 days) or FOLFOX [14]. The randomization took place postoperatively, so there was less dropout after surgery than has been seen in other trials.

At a median follow-up of 74 months, the FOLFOX group had a significantly higher six-year disease-free survival rate (68 versus 57 percent, HR 0.63, 95% CI 0.43-0.93), although treatment-related toxicity was also higher, and the improvement in six-year overall survival was modest and not statistically significant (78 versus 76 percent, HR 0.73, 95% CI 0.45-1.19) [15].

Can response to neoadjuvant therapy predict benefit? — We suggest that all patients undergoing preoperative long-course chemoradiotherapy or short-course RT receive postoperative chemotherapy, even if they have a pathologic complete response to neoadjuvant therapy. This approach is consistent with guidelines from the NCCN.

Retrospective series, registry reports, and at least one systematic review report excellent outcomes in patients who achieve a pathologic complete response after preoperative therapy for rectal cancer [16-18]. These data prompted questions about whether the addition of adjuvant chemotherapy represents overtreatment in this group, and they also have raised questions about whether radical surgery can be avoided in those who appear to have a complete clinical response following neoadjuvant chemoradiotherapy [19,20]. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Avoidance of radical surgery'.)

However, other data, all from retrospective studies, support benefit for adjuvant chemotherapy in this subgroup [21-25]. As an example, three separate observational cohort studies using the National Cancer Database to evaluate the association between adjuvant chemotherapy and overall survival among patients with a complete pathologic response following neoadjuvant chemoradiotherapy and surgery (ie, ypT0N0 disease) concluded that adjuvant chemotherapy does improve survival in this favorable subgroup [22-24]. In all three studies, patients who received adjuvant chemotherapy were matched by propensity score to those undergoing postresection observation only. However, in two of the analyses, the magnitude of purported benefit from chemotherapy seemed inexplicably high and could have represented an overestimation of treatment benefit [22,23]. Furthermore, approximately 70 percent of the patients in each of these two cohorts did not receive any adjuvant chemotherapy, which is more than double the rate of nontreatment in older patients with rectal cancer following neoadjuvant chemoradiotherapy in a Surveillance, Epidemiology, and End Results (SEER) database study [26], suggesting that patients and their clinicians were highly selective in making the decision to pursue or not pursue adjuvant chemotherapy.

Still other data suggest that there may in fact be greater benefit from adjuvant chemotherapy in nonresponders:

An analysis of data from five European trials of preoperative chemoradiotherapy for locally advanced rectal cancer concluded that the benefit of adjuvant chemotherapy was minimal for "responders" (ie, ypT0N0 disease) as compared with "nonresponders" (ie, ypT3N1 disease) (table 2) [27]. However, only two of the included trials (EORTC 22921 and the Italian trial [5,9]) actually randomly assigned patients to receive or not receive adjuvant chemotherapy; in the German Rectal Cancer Study Group and French Fédération Francophone de Cancérologie Digestive (FFCD) 9203 trials [28,29], all patients received adjuvant chemotherapy, while in the fifth trial, patients received adjuvant chemotherapy at the discretion of the treating clinician [30]. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Prognosis and extent of tumor regression'.)

Support for a greater intensity of chemotherapy (ie, an oxaliplatin-containing versus non-oxaliplatin-containing regimen) is also provided by the randomized phase II ADORE trial, which demonstrated preferential benefit for the oxaliplatin-containing regimen in patients with ypN2 stage III disease and those with minimally regressed tumors. These data are discussed in detail below. (See 'Choice of postoperative regimen' below.)

Guidelines from expert groups — Guidelines from expert groups regarding postoperative therapy in patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy or short-course RT are conflicting:

Guidelines from the NCCN [4] recommend that all such patients receive chemotherapy, even if they have a pathologic complete response to neoadjuvant therapy.

Updated guidelines from the European Society for Medical Oncology (ESMO) suggest that adjuvant chemotherapy be considered for yp stage III and "high-risk" yp stage II patients, although they emphasize that the level of scientific evidence for sufficient benefit is much lower in this setting than in colon cancer and is probably limited to a disease-free and not an overall survival benefit [31].

By contrast, experts convened by a European rectal cancer conference concluded that there is insufficient evidence on benefit of adjuvant chemotherapy after preoperative chemoradiotherapy to recommend its use [32].

Until additional data become available, we agree with the approach recommended by the NCCN.

Links to additional society guidelines can be found elsewhere. (See 'Society guideline links' below.)

Patients receiving total neoadjuvant therapy — The one setting in which we omit postoperative chemotherapy is in patients who received four months of neoadjuvant chemotherapy prior to surgery in conjunction with long-course chemoradiotherapy or short-course RT (ie, total neoadjuvant therapy).

Increasingly, total neoadjuvant therapy, in which the preoperative treatment includes not only RT but also four months of systemic chemotherapy (which would otherwise be given after resection), is seen as a reasonable alternative to long-course chemoradiotherapy alone for patients with locally advanced rectal cancer who are at high risk for a margin-positive resection (ie, T4 disease or an involved mesorectal resection margin) as well as for those with clearly node-positive disease and a low-lying rectal tumor, given the increased compliance with chemotherapy, the improved local control, and the ability to consider nonoperative treatment. Postoperative adjuvant therapy is generally omitted in patients who have received four months of preoperative systemic chemotherapy in conjunction with RT. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Total neoadjuvant therapy for locally advanced tumors'.)

CHOICE OF POSTOPERATIVE REGIMEN

Oxaliplatin versus non-oxaliplatin-containing regimens — There are several options for postoperative chemotherapy in patients who have had neoadjuvant chemoradiotherapy or short-course radiation therapy (RT), including those that are non-oxaliplatin containing (ie, leucovorin-modulated fluorouracil, fluoropyrimidine monotherapy, short-term infusional fluorouracil plus leucovorin [the de Gramont regimen (table 3)]) and oxaliplatin-containing (ie, short-term infusional fluorouracil plus leucovorin and oxaliplatin [FOLFOX (table 4)], or capecitabine plus oxaliplatin [CAPOX (table 5)]).

Some clinicians routinely utilize an oxaliplatin-based regimen for all patients who have received neoadjuvant chemoradiotherapy or short-course RT, regardless of postresection pathologic (yp) status, and this approach is supported by guidelines from the National Comprehensive Cancer Network (NCCN). However, largely based on the latest analysis of the ADORE trial, for most patients, we suggest a risk-adapted treatment strategy based upon the postoperative stage. We suggest an oxaliplatin-containing regimen preferentially for those patients with lesser degrees of tumor downstaging after preoperative chemoradiotherapy [ie, ypT3-4 or node-positive disease]). For other patients, either an oxaliplatin-containing or a non-oxaliplatin-containing regimen is acceptable. This approach is consistent with guidelines from European Society for Medical Oncology (ESMO). Other factors that should also be taken into account when deciding to pursue an oxaliplatin-based versus non-oxaliplatin-based adjuvant regimen are performance status, comorbidity, age, and patient preference. (See 'Guidelines from expert groups' below.)

There are few randomized phase III trials comparing different postoperative regimens after neoadjuvant chemoradiotherapy, and there is no consensus as to the best approach. Common fluoropyrimidine-based approaches include four months of the de Gramont regimen (table 3) or capecitabine alone, extrapolating from experience in adjuvant treatment of colon cancer. As with colon cancer, regimens containing irinotecan cannot be recommended [33]. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Less fit patients or a contraindication to oxaliplatin' and "Treatment protocols for small and large bowel cancer".)

The role of newer regimens containing oxaliplatin (eg, FOLFOX and CAPOX) has not yet been fully defined by adequately powered phase III trials. The following data are available:

ADORE trial – As noted above, direct evidence for the benefit of an oxaliplatin-containing regimen in patients with resected rectal cancer after neoadjuvant chemoradiotherapy was provided by the randomized phase II ADORE trial, in which 321 patients with curatively resected rectal cancer after neoadjuvant fluoropyrimidine-based chemoradiotherapy and yp stage II (ypT3-4N0) or III (ypT0-4N1-2) disease were randomly assigned to four months of monthly bolus fluorouracil/leucovorin or FOLFOX [14]. (See 'Benefit of postoperative chemotherapy' above.)

At a median follow-up of 74 months, the FOLFOX group had a significantly higher six-year disease-free survival rate (68 versus 57 percent, hazard ratio [HR] 0.63, 95% CI 0.43-0.93), although treatment-related toxicity was also higher, and the improvement in six-year overall survival was modest and not statistically significant (78 versus 76 percent, HR 0.73, 95% CI 0.45-1.19) [15]. In exploratory subgroup analysis, patients with ypN2 stage III disease and those with minimally regressed tumors derived the most benefit from FOLFOX (six-year disease-free survival 63 versus 48 percent), while there was no significant disease-free survival benefit in those with yp stage II or ypN1a disease. However, this was not a preplanned subgroup analysis, and the study was likely underpowered to detect significant differences in these small subgroups.

Other randomized trials – At least five published trials have examined the contribution of oxaliplatin to preoperative chemoradiotherapy; only two (the PETACC and CAO/ARO trials) compared an oxaliplatin-containing with a non-oxaliplatin-containing chemotherapy regimen both during RT and after surgery (table 6). Although there were no significant differences in overall survival in the PETACC or CAO/ARO trials favoring the addition of oxaliplatin either preoperatively or postoperatively, the CAO/ARO trial did report a significant improvement in three-year disease-free survival in patients receiving oxaliplatin-containing therapy both for preoperative chemoradiotherapy and in the adjuvant setting. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Oxaliplatin'.)

Meta-analysis – A meta-analysis of three randomized trials comparing fluorouracil-based adjuvant chemotherapy with oxaliplatin/fluorouracil-based adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery (the PETACC-6 [34], CAO/ARO [35], and ADORE trials [15]) also concluded that an oxaliplatin-containing regimen could improve disease-free survival (HR 0.85, 95% CI 0.73-0.99), albeit with a higher incidence of grade 3 or 4 nausea and vomiting [36]. There were no significant differences in terms of survival (only two trials, the ADORE and CAO/ARO trials, were included in this analysis), hematologic toxicity, and diarrhea.

Guidelines from expert groups — Guidelines from expert groups differ as to the selection of patients for oxaliplatin-based adjuvant therapy:

Consensus-based NCCN guidelines [4] for adjuvant therapy in patients who had neoadjuvant RT or chemoradiotherapy are based on the initial clinical stage, and they do not stratify recommendations according to the post-treatment pathologic stage:

For patients with clinical T3N0 tumors (table 1) and a clear circumferential resection margin or patients with an involved or threatened circumferential resection margin, a T4 primary tumor, or locally unresectable or medically inoperable disease, options include leucovorin-modulated fluorouracil, capecitabine, CAPOX, or FOLFOX; in all cases, the oxaliplatin-containing regimens are preferred.

For patients with clinical T1-3N1-2 tumors (table 1), an oxaliplatin-based regimen is recommended.

ESMO guidelines, which are based on pathologic stage, emphasize that following short-course RT or long-course chemoradiotherapy, individual randomized trials and meta-analyses [5,7,9,10,13] have not shown any benefit for a fluoropyrimidine alone [31]. The addition of oxaliplatin may improve disease-free survival [15,35,36], but results are not consistent [12], and there is no effect on overall survival in any trial. (See 'Benefit of postoperative chemotherapy' above.)

The guidelines state that it is reasonable to consider adjuvant chemotherapy in rectal cancer patients with yp stage III and "high-risk" yp stage II tumors, although they do not elaborate on the specific characteristics that define "high-risk" yp stage II tumors. The decision on whether to choose a fluoropyrimidine alone or combined with oxaliplatin should be risk balanced, taking into account both the predicted toxicity for a particular patient and the risk of relapse; the decision should be made jointly by the clinician and patient.

CHEMOTHERAPY DOSING FOR OBESE PATIENTS — Most chemotherapy drugs are dosed on the basis of body surface area. Doses for persons with obesity are sometimes calculated based on ideal rather than actual body weight, a practice for which there is no scientific basis. Underdosing of chemotherapy may have adverse clinical consequences for persons with obesity with rectal cancer, as was shown in the Intergroup 0114 trial [37]. (See "Adjuvant therapy for resected rectal adenocarcinoma in patients not receiving neoadjuvant therapy", section on 'Agents not used'.)

Guidelines from The American Society of Clinical Oncology (ASCO) recommend that full weight-based cytotoxic chemotherapy doses be used to treat persons with obesity who have cancer, particularly when the goal of treatment is cure [38]. Dose adjustments should be based on an individual patient's treatment-related toxicity. (See "Dosing of anticancer agents in adults", section on 'Dosing for overweight/obese patients'.)

ADJUNCTIVE THERAPIES — The benefits of diet and exercise, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), vitamin D, and coffee consumption on cancer outcomes are discussed separately. (See "Adjunctive therapy for patients with resected early stage colorectal cancer: Diet, exercise, NSAIDs, and vitamin D" and "The roles of diet, physical activity, and body weight in cancer survivors".)

POSTTREATMENT SURVEILLANCE AND SURVIVOR ISSUES — Recommendations for posttreatment cancer surveillance and issues that arise in long-term survivors of rectal cancer (genitourinary problems, bowel and anorectal dysfunction) are discussed in detail elsewhere. (See "Post-treatment surveillance after colorectal cancer treatment" and "Approach to the long-term survivor of colorectal cancer".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Colorectal cancer".)

SUMMARY AND RECOMMENDATIONS

Indications – Although the benefits are controversial, following resection, we suggest that all patients who underwent neoadjuvant chemoradiotherapy or short-course radiation therapy (RT) receive four months of adjuvant chemotherapy, regardless of the pathologic findings (Grade 2C). However, practice is variable, and at some institutions, patients with a pathologic complete response after induction therapy are not routinely offered postoperative chemotherapy. (See 'Following neoadjuvant short-course RT or long-course chemoradiotherapy' above.)

For patients who received four months of initial chemotherapy in conjunction with preoperative chemoradiotherapy or short-course RT (ie, total neoadjuvant therapy), we omit adjuvant chemotherapy. (See 'Patients receiving total neoadjuvant therapy' above.)

Choice of regimen – The best regimen in this situation is not conclusively established. Reasonable options include regimens that are oxaliplatin-containing (eg, short-term infusional fluorouracil plus leucovorin and oxaliplatin [FOLFOX (table 7)], capecitabine plus oxaliplatin [CAPOX (table 8)]), and those that are non-oxaliplatin-containing (eg, short-term infusional fluorouracil plus leucovorin [the de Gramont regimen (table 3)]), or capecitabine alone. (See "Treatment protocols for small and large bowel cancer".)

Some clinicians routinely utilize an oxaliplatin-based regimen for all patients who have received neoadjuvant chemoradiotherapy, regardless of postresection pathologic (yp) status, an approach that is consistent with consensus-based National Comprehensive Cancer Network guidelines. However, for most patients, largely based on the latest analysis of the ADORE trial, we prefer a risk-adapted treatment strategy based upon the postoperative stage. We suggest an oxaliplatin-containing rather than a non-oxaliplatin-containing regimen for those patients with lesser degrees of tumor downstaging after preoperative chemoradiotherapy (ie, ypT3-4 or node-positive disease) (Grade 2C). For other patients, either an oxaliplatin or a non-oxaliplatin-based regimen is acceptable. This approach is consistent with guidelines from the European Society for Medical Oncology. Other factors that should also be taken into account when deciding to pursue an oxaliplatin-based versus non-oxaliplatin-based adjuvant regimen are performance status, comorbidity, age, and patient preference. (See 'Choice of postoperative regimen' above.)

Dosing in persons with obesity – Full weight-based cytotoxic chemotherapy doses should be used to treat persons with obesity who have cancer, particularly when the goal of treatment is cure. Dose adjustments during therapy should be based upon individual patient's treatment-related toxicity. (See 'Chemotherapy dosing for obese patients' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David P Ryan, MD, who contributed to earlier versions of this topic review.

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Topic 118234 Version 21.0

References

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