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The Oncologist, Vol. 5, No. 3, 250-259, June 2000
© 2000 AlphaMed Press

The Consequences of Diarrhea Occurring During Chemotherapy for Colorectal Cancer: A Retrospective Study

R.B. Arbucklea, S.L. Hubera, C. Zackerb

a University of Texas M.D. Anderson Cancer Center, Division of Pharmacy—Department of Pharmacoeconomics, Houston, Texas, USA; b Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

Correspondence: Rebecca B. Arbuckle, M.S., R.Ph., University of Texas M.D. Anderson Cancer Center, Department of Pharmacoeconomics, Division of Pharmacy, 1515 Holcombe Boulevard, Box 706, Houston, Texas 77030-4095, USA. Telephone: 713-745-1413; Fax: 713-791-1320; e-mail: barbuckle{at}notes.mdacc.tmc.edu


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 Conclusions
 References
 
Purpose. Diarrhea is one of the dose-limiting toxicities associated with chemotherapy agents in treatment regimens for colorectal cancer. The objectives of this study were to analyze the impact of all grades of diarrhea on clinical decisions for patients receiving treatment for colorectal cancer by characterizing the diarrhea that occurred, quantifying changes in chemotherapy treatment, identifying methods to treat diarrhea, and determining the economic impact.

Patients and Methods. We retrospectively reviewed the treatment of 100 consecutive patients with colorectal cancer who experienced diarrhea during the course of chemotherapy. The diarrhea was documented in the progress notes and graded according to National Cancer Institute Common Toxicity Criteria. Changes in chemotherapy treatment and resource utilization associated with diarrhea were recorded.

Results. The 100 patients received 673 chemotherapy cycles, of which 45% ± 2% were associated with diarrhea. Approximately 52% of patients experienced diarrhea of grades 3 or 4, and 56 patients underwent 66 modifications in their chemotherapy treatment, such as dose reductions (22), delays in therapy (8), discontinuations of therapy (15), or multiple changes (11). Thirty-seven patients consumed resources beyond oral antidiarrheals to control diarrhea: 14 patients received emergency outpatient treatment, 23 patients were hospitalized, 21 patients received intravenous fluids, and one death due to dehydration was reported.

Discussion and Conclusion. Diarrhea was a significant consequence of colorectal chemotherapy, with the majority of patients experiencing grades 3 or 4 diarrhea and 56% of all patients also modifying their chemotherapy treatment. Even mild diarrhea of grades 1 and 2 was associated with changes in treatment in 11% of patients; thus, diarrhea of all grades should be recognized and treated appropriately to maintain full-dose chemotherapy.

Key Words. Colorectal neoplasms • Diarrhea • Chemotherapy • Adjuvant • Receptors • Somatostatin • Retrospective studies • Fluorouracil • Carnitine O-palmitoyltransferase • Octreotide


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 Conclusions
 References
 
The dose-limiting toxicity of many chemotherapy agents used in the treatment of colorectal cancer is diarrhea, with the risk for chemotherapy-induced diarrhea (CID) significantly higher for regimens that contain fluoropyrimidines (e.g., 5-fluorouracil [5-FU]) and irinotecan (CPT-11) and with reported incidences as high as 50% to 80% [1]. In an effort to control colorectal cancer and sustain remission, adjuvant chemotherapy and radiation have also been used to eliminate microscopic tumor foci and thereby extend life expectancy in patients with colorectal cancer [2]. However, these adjuvant treatments can frequently be more aggressive regimens to increase the potential of further remission or cure, and they also carry increased risks for development of CID [1]. Researchers continue to investigate chemotherapy regimens and dosing schedules that would provide increased efficacy and decreased toxicity in treating advanced colorectal cancer, and a variety of drugs are currently being tested in experimental clinical trials (e.g., capecitabine, oxaliplatin, and raltitrexed) [3-17].

Despite reports of diarrheal complications tabulated in controlled clinical trials of chemotherapeutic agents, the number of patients in oncology clinical settings affected by diarrhea and the potential seriousness of even mild diarrhea are sometimes unrecognized or neglected [18, 19]. CID can be a debilitating and potentially life-threatening toxicity, since fluid and electrolyte loss associated with persistent or severe diarrhea can result in electrolyte imbalances, renal insufficiency, and extreme dehydration. These, among other factors, contribute to the morbidity and mortality associated with CID [1]. In addition to its direct effect on patient health, CID can indirectly affect patient treatment alternatives by requiring dosage reductions or treatment delays. Reducing or delaying the administration of the next cycle of chemotherapy in response to dose-limiting toxicity may decrease the therapeutic effect of treatment [20]. CID can also have economic consequences inasmuch as treating severe diarrhea may require frequent emergency room visits or hospitalization. Finally, CID can impact patients directly by reducing both patient compliance and patient quality of life [1].

The choice of antidiarrheal treatment is influenced by a number of factors, including severity of diarrhea, ease of administration, and cost. The most commonly used agents for nonspecific symptomatic treatment of CID include opiate agonists such as loperamide and diphenoxylate [19, 21]. These agents act by decreasing the release of acetylcholine from the gut and thus slowing intestinal motility. Newer antidiarrheal agents, such as the somatostatin analog octreotide and {alpha}-2 adrenoreceptor agonists, have also been shown to be effective in the control of diarrhea in severe or refractory cases [21]. Guidelines have been published that provide assistance to clinicians and nurses in choosing treatment pathways for CID [1]. However, challenges still facing clinicians and nurses in treating patients with chemotherapy are providing comprehensive patient instruction, preventing the development of diarrhea, and proactively responding to all cases of diarrhea [1, 19, 22-26].

No specific prognostic factors had been described to help identify patients at risk for development of CID until an Italian study of 5-FU–associated diarrhea occurring during treatment of colorectal cancer was reported. Even from this study, only the presence of primary tumor, previous episodes of CID, and summer season were identified as significant risk factors for the development of diarrhea [18]. Further analysis of the impact of diarrhea on oncology regimens, patient response to CID, and relationships of treatment regimens and tumor stage with the severity of diarrhea would provide information to aid in clinical decisions during oncology therapy. Accordingly, this retrospective study will characterize the diarrhea that occurred in 100 patients treated for colorectal cancer at University of Texas M.D. Anderson Cancer Center (UTMDACC). This study will also quantify the frequency with which CID and changes in chemotherapeutic treatment occurred and obtain qualitative information about the types and extent of resources consumed to manage CID. This was not an efficacy trial; hence, clinical outcomes of chemotherapy or CID treatment were not investigated.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 Conclusions
 References
 
Study Sample
Records of patients who registered at UTMDACC between May 1995 and February 1998 were retrospectively reviewed. Patients were included in the study if they met the following requirements: A) a biopsy or pathologically confirmed diagnosis of colorectal cancer; B) received chemotherapy treatment at UTMDACC; C) experienced diarrhea during at least one chemotherapy cycle, and D) were followed at UTMDACC. The study sample consisted of the first 100 patients who met all four of these requirements.

Data Collection
Demographic information for the patients was obtained through a search of the database maintained by Medical Informatics at UTMDACC, including: A) gender; B) age at diagnosis; C) race; D) site of primary neoplasm; E) grade of tumor at diagnosis; F) histology of neoplasm; G) previous treatment, and H) treatment at UTMDACC in the first four months. Additional patient data were collected from progress notes and patient chart information by one of the authors (R.A.). The following information was extracted for each patient: A) chemotherapy regimen, dose, and date of registration at UTMDACC; B) grade(s) of diarrhea experienced; C) chemotherapy changes considered to be due to CID, and D) resources consumed for management of the diarrhea.

Data Analysis
Each episode of diarrhea occurring over all cycles of chemotherapy for each patient was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) (grade 0 = no diarrhea; grade 1 [mild] = increase of 2 to 3 stools per day; grade 2 [moderate] = increase of 4 to 6 stools per day, or nocturnal stools, or moderate cramping; grade 3 [severe] = increase of 7 to 9 stools per day, or incontinence, or severe cramping; grade 4 [life-threatening] = increase of >=10 stools per day, or grossly bloody diarrhea, or need for parenteral support). All episodes of diarrhea of any and all grades, which occurred over all cycles of chemotherapy, were recorded for each patient.

Over all chemotherapy cycles, the following changes were noted for each patient: A) dosing decrease; B) dosing delay, and C) discontinuation of therapy. A switch to a completely different chemotherapy regimen was not considered as a discontinuation, as the reason for this type of change could not always be determined from chart review.

Over all the cycles of chemotherapy, the following types of resource utilization for diarrhea were noted for each patient: A) oral antidiarrheals; B) octreotide; C) emergency outpatient treatment; D) hospitalizations, and E) fluids given intravenously.

Statistical Analysis
Statistical analysis was performed using Pro-Stat for Windows® (Poly Software International; Salt Lake City, UT; http://www.polysoftware.com). Different sample distributions of grades of diarrhea were compared using the Kolmogorov-Smirnov two-tailed test (K-S test), a nonparametric test that makes no assumptions about the underlying distributions [27]. Mean values are reported ± SE (standard error).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 Conclusions
 References
 
Patient Demography
The demographic characteristics of the sample of 100 patients are listed in Table 1Go. Patients were mostly male (67%), white (79%), and middle-aged (mean 56.0 ± 1.1 years), with a diagnosis of rectal cancer (45%). Most patients (63%) received only one chemotherapy regimen for all cycles of chemotherapy, but the rest received multiple regimens, usually administered sequentially (Table 2Go). The most common regimen was 5-FU + leucovorin (LV), which was the sole therapy for 56 patients and was followed by other regimens for an additional 30 patients. The second most common regimen was CPT-11, which was received by a total of 33 patients. Less common regimens were continuous infusion 5-FU (5-FUCI) (n = 16), capecitabine (n = 10), and ftorafur (a prodrug of 5-FU) combined with uracil (UFT) (n = 4).


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  		Table 1. Description of study population
 

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  		Table 2. Number of patients receiving different chemotherapy regimens either as sole therapy or as combination therapy over all cycles of chemotherapy
 
Data Evaluation
Due to the complexity of data collected, the occurrence and grade of diarrhea were analyzed in relationship to a number of factors, including: the chemotherapy cycle number, early compared to late chemotherapy cycles, the chemotherapy regimen used, overall treatment regimens, site or stage of tumor, changes or modifications in chemotherapy regimens, and the pharmacoeconomic impact or resource utilization.

Characterization of Diarrhea Occurring Over Treatment Course by Chemotherapy Cycle
The occurrence of diarrhea of any grade over all cycles of chemotherapy was noted for each patient. The percentage of chemotherapy cycles associated with the occurrence of diarrhea of any grade (National Cancer Institute [NCI] [http://www.nci.nih.gov] grades 1 to 4) was calculated for each patient, and the results are shown in Figure 1Go. The 100 patients received a total of 673 cycles of chemotherapy (mean of 6.7 ± 0.4 [± SE] cycles per patient), and 45% ± 2% of these cycles were associated with diarrhea. For example, the data point at the extreme right of Figure 1Go represents a patient who received 22 cycles of chemotherapy, and diarrhea (NCI grades 1 to 4) occurred during 12 of these cycles (55%). Patients who received fewer than seven cycles of chemotherapy were more likely to suffer from diarrhea than those who received seven or more cycles of therapy (52.0% ± 3.4% versus 32.5% ± 2.4% of cycles associated with diarrhea, respectively, p < .001, K-S test).



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  		Figure 1. Relationship between the total number of chemotherapy cycles for each patient and the percentage of chemotherapy cycles associated with any grade of diarrhea (1 to 4). For example, the data point at the extreme right represents a patient who received 22 cycles of chemotherapy, and diarrhea (NCI grades 1 to 4) occurred during 12 of these cycles (55%). Most of the data points for total number of chemotherapy cycles >8 correspond to single patients; however, for cycles <8, the data points usually represent multiple patients (range 1 to 9).

 
Early Versus Late Occurrence of Diarrhea Over Treatment Course by Chemotherapy Cycle
Frequency distributions for occurrence of the different grades of diarrhea (NCI grades 1 to 4) during chemotherapy treatment for each patient were evaluated for both 5-FU + LV and CPT-11 to determine whether diarrhea was more likely to occur early in treatment rather than later (Figs. 2 and 3GoGo). If a patient received more than one chemotherapy regimen, then the first cycle was considered to be the first time a patient received that particular regimen. For example, in Figure 2Go, 86 patients received the first cycle of chemotherapy with 5-FU + LV. During that first cycle, diarrhea of NCI grades 1 to 4 was experienced by 18, 13, 9, and 4 patients, respectively. The remaining 42 patients did not experience any diarrhea during that cycle (i.e., NCI grade 0). Five patients discontinued treatment with 5-FU + LV after cycle 1, with 81 patients receiving a second cycle of 5-FU + LV. For both regimens CPT-11 and 5-FU + LV, more instances of diarrhea occurred in the first few cycles of therapy than occurred later.



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  		Figure 2. Frequency distribution of the occurrence of diarrhea during different cycles of chemotherapy with 5-fluorouracil (5-FU) + LV. n refers to the total number of patients who received that cycle of chemotherapy with 5-FU + LV. For example, 86 patients received the first cycle of chemotherapy, and during that first cycle, diarrhea of grades 1 to 4 was experienced by 18, 13, 9, and 4 patients, respectively. The remaining 42 patients did not experience any diarrhea during cycle 1 (e.g., NCI grade 0). Five patients then discontinued treatment, so that 81 patients received a second cycle of 5-FU + LV.

 


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  		Figure 3. Frequency distribution of the occurrence of diarrhea during different cycles of chemotherapy with CPT-11. n refers to the total number of patients who received that cycle of chemotherapy with CPT-11. For example, 33 patients received the first cycle of chemotherapy, and during that first cycle, diarrhea of grades 1 to 4 was experienced by 7, 9, 1, and 8 patients, respectively. The remaining 8 patients did not experience any diarrhea during cycle 1 (e.g., NCI grade 0). Seven patients then discontinued treatment, so that 26 patients received a second cycle of CPT-11.

 
Occurrence of Diarrhea by Chemotherapy Treatment Regimen
The various chemotherapy regimens were associated with different frequency distributions of diarrhea when all cycles were examined including cycles with no diarrhea (Table 3Go). Cycles in which no diarrhea occurred corresponded to NCI grade 0, and the highest grade was selected if diarrhea of different grades occurred during the same cycle of chemotherapy for a particular patient. The mean grade of diarrhea was lowest for 5-FUCI and UFT (mean NCI grades: 0.70 ± 0.18 and 0.72 ± 0.25, respectively) and highest for capecitabine and CPT-11 (1.10 ± 0.24 and 1.15 ± 0.16, respectively). The mean grade of diarrhea was intermediate for 5-FU + LV at 0.78 ± 0.06 and the overall distribution of diarrhea for 5-FU + LV was statistically significantly different than it was for the other chemotherapy regimens (p < .0002, K-S test). In summary, the relative probabilities of the occurrence of diarrhea were 5-FUCI {cong} UFT < 5-FU + LV < capecitabine {cong} CPT-11.


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  		Table 3. Relationship between chemotherapy regimen and highest grade of diarrhea experienced by each patient for every cycle of chemotherapy
 
Incidence of Diarrhea by Grade for the Overall Treatment Regimens
The 100 patients were analyzed by the highest grade of diarrhea that occurred over all cycles of chemotherapy (24, 24, 22, and 30 for NCI grades 1 to 4, respectively), with a mean value for the highest grade of diarrhea of 2.58 ± 0.12. Since more than half of the patients (52%) experienced severe diarrhea (NCI grades 3 or 4) during their chemotherapy, the overall treatment was examined for any association with the highest grade of diarrhea experienced by the patients. There were no statistically significant differences in the distributions of highest grade of diarrhea based on treatment (previous treatment plus treatment at UTMDACC during the first four months after registration at UTMDACC). Mean grades of diarrhea ranged from 2.00 ± 0.41 for patients who had surgery only (followed by chemotherapy more than four months after registration at UTMDACC) to 2.76 ± 0.20 for patients who had surgery, radiotherapy, and chemotherapy (data not shown).

Incidence of Diarrhea by Site of Tumor or Stage of Tumor
There were no statistically significant differences in the distributions of highest grade of diarrhea based on site of primary tumor, with mean values of 2.29 ± 0.32 for sigmoid colon, 2.47 ± 0.26 for cecum, 2.73 ± 0.18 for rectum, and 2.93 ± 0.30 for rectosigmoid junction. Distributions of highest grade of diarrhea as a function of stage of tumor at diagnosis were also similar, with mean values ranging from 2.00 ± 0.21 for patients with local tumors to 3.00 ± 0.58 for patients who showed no evidence of disease after treatment (Table 4Go). While most of these distributions for diarrhea as a function of stage of tumor at diagnosis were not statistically different, there was a tendency for tumors that had metastasized to be associated with more severe diarrhea than tumors that were localized (mean NCI grades 2.72 ± 0.16 versus 2.00 ± 0.21, respectively, p = .01, K-S test).


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  		Table 4. Relationship between stage of tumor at diagnosis and highest grade of diarrhea experienced by each patient
 
Changes in Chemotherapy Treatment
Fifty-six patients who experienced CID underwent 66 changes in their chemotherapy treatment. These changes included dose reductions (22), delays in therapy (8), and discontinuations of therapy (15). Two or more changes were seen in 11 patients. Forty-four patients had no changes made to their chemotherapy treatment. The relationship between change in chemotherapy treatment and highest grade of diarrhea experienced by each patient was examined (Table 5Go). The mean grades of diarrhea for patients who experienced changes ranged from 2.25 ± 0.25 for patients with dosing delays to 3.73 ± 0.14 for patients with two or more changes. However, the mean grade of diarrhea for patients with no changes was 1.78 ± 0.14. This distribution was significantly different from those for patients with changes (p < .002, K-S test). Thus, patients with higher grades of diarrhea tended to have changes to their chemotherapy treatment. It is noteworthy that 11 patients with low grades of diarrhea (NCI grades 1 or 2) also underwent changes in chemotherapy treatment. At least three of the four patients with grades 1 or 2 diarrhea who terminated chemotherapy did so at their own request.


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  		Table 5. Relationship between change in chemotherapy treatment and highest grade of diarrhea experienced by each patient
 
Resource Consumption
Thirty-seven patients consumed additional resources beyond oral antidiarrheals to treat their diarrhea; specifically, 14 patients had emergency outpatient treatment, 23 patients were hospitalized, 21 patients received intravenous fluids to treat dehydration, and seven patients received octreotide. The 63 patients who did not utilize resources beyond oral antidiarrheals tended to have lower grades of diarrhea, with a mean grade of 2.19 ± 0.13 (Table 6Go). On the other hand, the patients using additional supportive resources had mean grades of diarrhea ranging from 3.29 to 3.44, with these distributions statistically significantly different from those of patients who consumed no additional resources (p < .002, K-S test). Seven patients with a mean grade of diarrhea of 3.43 ± 0.30 were given intravenous octreotide to treat the diarrhea.


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  		Table 6. Relationship between resources consumed other than oral antidiarrheals and highest grade of diarrhea experienced by each patient
 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
Conclusions
 References
 
Our study reinforces previous reports that CID is a prevalent and severe toxicity associated with a variety of sole agents and combination chemotherapy regimens used for treatment of colorectal cancer. Although all patients in our study experienced diarrhea, only one patient was known to have died as a consequence of dehydration, 52% of the patients experienced severe diarrhea (grades 3 or 4), and approximately 45% of the chemotherapy cycles were associated with diarrhea. After considering the various chemotherapy regimens in our study sample, the relative probabilities of the occurrence of diarrhea were 5-FUCI {cong} UFT < 5-FU + LV < capecitabine {cong} CPT-11. This sequence of relative gastrointestinal toxicities of the different chemotherapy regimens agrees with previously published results. For example, Hoff et al. reported that severe diarrhea occurred less frequently in patients receiving UFT and oral LV than in patients receiving 5-FU [28]. Van Cutsem et al. studied CPT-11 versus infusional 5-FU in patients refractory to 5-FU, and found a higher toxicity for CPT-11 (NCI grades 3 and 4 diarrhea: 22% for CPT-11 versus 11% for 5-FU) [29].

The occurrence of diarrhea strongly impacted clinical decisions about chemotherapy regimens, as 56% of patients underwent changes in treatment. These included dose reductions in 22% of patients, delays in administration of subsequent drug cycles in 8%, and total discontinuations of therapy in 15% of patients. More than one change was experienced by 11% of patients. Because changes in actual chemotherapeutic agent were not considered, these numbers may actually underrepresent the impact of diarrhea on chemotherapy.

An important finding was that even low grades of diarrhea could adversely affect chemotherapy treatment, as 11% of patients who had changes in treatment had lower grade (1 or 2) diarrhea.

Since mild diarrhea is sometimes empirically discounted as a major side effect, these data on treatment modifications underscore the importance any grade of diarrhea may have on proposed clinical management. Overall, the occurrence of diarrhea has a negative influence on the delivery of optimal chemotherapy and patient acceptance of that chemotherapy.

An unexpected result of our retrospective survey was that a majority (52%) of the patients with diarrhea had the higher grade (3 or 4) diarrhea. Our studies included data from five different chemotherapy drugs used as sole therapy or in combination therapy. Most studies on specific agents indicate that the percentage of patients with diarrhea who have severe diarrhea is less than 50%. For example, Kohne et al. report that, in a clinical study of high-dose continuous infusion of 5-FU + LV, the distribution of patients exhibiting diarrhea of NCI grades 1 to 4 was 29%, 17%, 9%, and 12%, respectively [30]. Studies comparing continuous infusion versus bolus dosing of 5-FU have been reported to show reduced gastrointestinal toxicity for continuous 5-FU [30]. In other words, 21% of the patients with diarrhea had grades 3 or 4. Similarly, Saliba et al. report that in a study of CPT-11 in patients with colorectal cancer, 82% had diarrhea of all grades (NCI grades 1 to 4) and 32% had severe diarrhea (grades 3 or 4) [31]. Similar results were obtained by Van Cutsem et al. [32]. Since most oncology clinics use multiple agents and regimens similar to those reviewed in our study sample, the incidences of diarrhea reported from clinical trials designed to determine safety and efficacy for a single drug or regimen might be underestimates of diarrhea in the oncology clinic setting.

Our result that 23% of individuals who experience diarrhea during chemotherapy will eventually be hospitalized agrees quite well with previously published results. For example, the rate of hospitalization for toxicity related to chemotherapy has been reported to be 27% for CPT-11 and 21% to 31% for 5-FU, both numbers referring to the entire population of patients [22]. A recent study of the incidence of hospitalization for 5-FU toxicity in colorectal cancer reported that 31% of the patients experienced hospitalizations [33]. Even though these published results are for the total population of patients undergoing chemotherapy in various clinical trials and our data are for a subset of patients who experience diarrhea, the percentages of patients hospitalized are very similar, indicating that our set of patients is probably not atypical of the total population.

Our results evaluating factors that influence the development of CID (e.g., most factors like site of tumor, etc., are not associated with diarrhea) also agree with published reports. When patients were identified by the highest grade of diarrhea that occurred over all their cycles of chemotherapy, the mean grade had little or no correlation with the overall treatment, the site of primary tumor, or the stage of tumor at diagnosis. The lack of correlation with these variables reflects similar results from an Italian study done with 5-FU–associated diarrhea [18]. This study on factors influencing diarrhea during treatment with 5-FU found that the following parameters were not correlated with diarrhea: age, sex, chemotherapeutic regimen, site of the primary tumor, presence of colostomy, and time since surgery. The same study also found that diarrhea was more likely to occur in the first two cycles versus three or more, thus corroborating our data indicating the higher incidence of diarrhea earlier in the chemotherapy cycles [18]. However, our study also followed severity according to treatment cycle and showed that severe high-grade diarrhea can occur during any treatment cycle.

A final observation is that a sizable proportion of patients with diarrhea may utilize resources beyond oral antidiarrheals. This additional consumption of resources has significant economic consequences, which must be considered in today's environment of balancing costs with effective treatments. For example, at UTMDACC, the average cost for emergency outpatient treatment is $250 per admission, and hospitalization costs are approximately $850 per day for room and board only. The total cost expended on both hospital and emergency care resource managment for the 100 patients in this study was $90,550. Thus, proactive, aggressive, prophylactic treatment for CID may provide both economic benefits and improved patient quality of life. Studies are under way to evaluate the potential benefits of better control or prevention of diarrhea during chemotherapy treatment.


   Conclusions
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusions
References
 
Our results have several implications for the treatment of colorectal cancer with chemotherapy. One is that all grades of diarrhea can impact patient treatment and quality of life, not just grades 3 and 4. While most clinicians recognize the need to aggressively treat or prevent severe diarrhea, persistent lower grades can be so burdensome to patients that they choose to discontinue treatment, as our results have shown. Severe diarrhea can occur during any chemotherapy cycle and can be immediate or delayed; therefore, a proactive and aggressive treatment plan, preferably with a prophylactic component for prevention of diarrhea, should be formulated using current treatment guidelines for CID outlined in Wadler et al. [1]. Eventually, validated methods of assessing diarrhea and its consequences may become standard components of clinical trials and lead to the further refinement of evidence-based, cost-effective treatment algorithms.


   Acknowledgments
 
This study was sponsored by Novartis Pharmaceuticals Corporation (http://www.pharma.novartis.com). Statistical analyses were performed by Carol Lewis, Ph.D. The patient population was identified through a search of the databases maintained by Medical Informatics.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusions
 References
 

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Received February 28, 2000; accepted for publication April 16, 2000.




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