Participant recruitment and characteristics
A total of 96 patients were assessed for eligibility for this study during the data collection period. Fifty-one patients were enrolled in the study. The patient recruitment process is shown in Fig. 3.
Twenty-six patients were analyzed in the intervention group and 25 in the control group. Table 2 shows the socio-demographic and disease-related patient characteristics. The two study groups were well balanced.
Table 2
Socio-demographic and disease-related patient characteristics
| | Intervention group (n = 26) | | Control group (n = 25) |
| | n | % | | n | % |
Age (years) | ≤ 50 | 5 | 19.2 | | 5 | 20.0 |
51–60 | 11 | 42.3 | | 11 | 44.0 |
61–70 | 8 | 30.8 | | 5 | 20.0 |
71–80 | 2 | 7.7 | | 4 | 16.0 |
Gender | Female | 21 | 80.8 | | 22 | 88.0 |
Education | High school or less | 13 | 50.0 | | 12 | 48.0 |
Some college | 3 | 11.5 | | 3 | 12.0 |
College graduate or more | 7 | 26.9 | | 8 | 32.0 |
Missing | 3 | 11.5 | | 2 | 8.0 |
Disease site | Breast cancer | 13 | 50.0 | | 11 | 44.0 |
Colorectal cancer | 5 | 19.2 | | 4 | 16.0 |
Ovarian cancer | 2 | 7.7 | | 4 | 16.0 |
Lung cancer | 2 | 7.7 | | 2 | 8.0 |
Other | 4 | 15.4 | | 4 | 16.0 |
Time since diagnosis | < 6 months | 17 | 65.4 | | 18 | 72.0 |
6–24 months | 5 | 19.2 | | 5 | 20.0 |
> 24 months | 4 | 15.4 | | 2 | 8.0 |
Treatment regimen1 | FEC-Doc | 5 | 19.2 | | 4 | 16.0 |
FOLFOX4 | 4 | 15.4 | | 2 | 8.0 |
TAC | 3 | 11.5 | | 0 | 0.0 |
EC-Doc | 1 | 3.8 | | 2 | 8.0 |
DC | 1 | 3.8 | | 2 | 8.0 |
FUFOX | 1 | 3.8 | | 2 | 8.0 |
GC-B | 0 | 0.0 | | 3 | 1.0 |
Other | 11 | 42.3 | | 10 | 40.0 |
Treatment modification | Dose reduction | 2 | 7.7 | | 0 | 0.0 |
Therapy interruption | 5 | 19.2 | | 7 | 28.0 |
Change of therapy | 4 | 15.4 | | 2 | 8.0 |
Discontinuation of therapy | 2 | 7.7 | | 2 | 8.0 |
Number of observed treatment cycles | 5 | 16 | 61.5 | | 19 | 76.0 |
3–4 | 5 | 19.2 | | 3 | 12.0 |
1–2 | 3 | 11.5 | | 3 | 12.0 |
0 | 2 | 7.7 | | 0 | 0.0 |
Number of simultaneously taken / administered drugs in total | 6–10 | 10 | 38.5 | | 11 | 44.0 |
11–15 | 13 | 50.0 | | 12 | 48.0 |
> 15 | 3 | 11.5 | | 2 | 8.0 |
1Therapy regime: FEC-Doc = Fluorouracil + Epirubicin + Cyclophosphamide followed by Docetaxel; FOLFOX4 = Calcium folinate + Fluorouracil + Oxaliplatin; TAC = Docetaxel + Doxorubicin + Cyclophosphamide; EC-Doc = Epirubicin + Cyclophosphamide followed by Docetaxel; DC = Docetaxel + Cyclophosphamide; FUFOX = Fluorouracil + Calcium folinate + Oxaliplatin; GC-B = Carboplatin + Gemcitabin + Bevacizumab |
Module application
Twenty-six patients were randomized to get the MuMM intervention. These patients were counseled in total 66 times by the pharmacist. The mean duration of the patient interviews was 16 minutes with a range of 5 to 50 minutes. Every patient received a written medication plan.
The supplementary modules for mucositis, fatigue, nausea/vomiting, and pain were applied in 18, 18, 16, and 11 patients, respectively. Most patients had three active supplementary modules and four patients had no active supplementary module.
Semi-structured interviews
The interviews with the involved physician, nurse, and pharmacist showed that all three were satisfied with the preparation process. All of them used the written leaflets for patient information and counseling. The physician appreciated the pharmacist very much for the comprehensive medication review and identification of drug-related problems. All involved professionals emphasized that the patient interviews during the intervention intensified the involvement of the patients. However, the transfer of the intervention to clinical practice revealed some problems and barriers interfering with the optimal application of the multiprofessional medication management. From the physician’s point of view there was often not enough time for proper patient interviews and documentation regarding symptoms and adverse drug reactions as demanded for the medication management and as requirement for the supplementary modules of the intervention. The nurse felt herself only poorly integrated into the multiprofessional health care team and in some occasions did not know if she should contact the physician or the pharmacist. The pharmacist perceived the communication with the physician as limited and as mainly taking place within the written patient records. She missed a feedback from the physician concerning her documentation of the medication management in the patient records.
All three interviewed health care providers suggested changes for improvement of the MuMM intervention. These were:
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to use a digital hub for central documentation of patient data with access from the outpatient ward as well as from the pharmacy to optimize and facilitate communication,
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to implement patient consultation via telephone by the pharmacist or a regular consultation-hour by the pharmacist for patients at the outpatient ward once a week,
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to include oral anticancer therapies and further symptoms like neuropathic symptoms into the MuMM intervention, and
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to implement meetings with all participating health care providers on a regular basis to discuss specific patient cases and to discuss the further care process for the individual patient.
Symptom burden
Figure 4 shows the proportion of patients per cycle and treatment group suffering from nausea, vomiting, mucositis, fatigue, or pain of PRO-CTCAE scores ≥ 75, corresponding to grade 3 or 4 (severe or very severe; frequently or almost constantly; quite a bit or very much) symptomatic toxicity. There was a relatively high symptom burden at baseline for fatigue and pain; 20% of the patients in the control group and 8% of the patients in the intervention group reported PRO-CTCAE scores ≥ 75 for both symptoms at cycle 0. In total, a median of seven patients (34%, range 5–9) in the intervention group and of eight patients (43%, range 6–14) in the control group suffered from toxicity of PRO-CTCAE score ≥ 75 nausea, vomiting, mucositis, fatigue, or pain within the five cycles of chemotherapy.
To analyze the effect of the MuMM intervention on symptom burden we used GEE models. Table 3 shows the parameter estimates and the p values obtained from the GEE models to analyze the associations between the defined predictor variables and the occurrence of the symptoms nausea, vomiting, mucositis, fatigue, or pain. No statistically significant associations could be found for any of the symptoms with the variables treatment group, therapy cycle, or treatment modification except for the association between nausea and the therapy cycle (1 to 3) as well as mucositis and the therapy cycle (1 to 5).
Table 3
Association between predictor variables and the outcomes nausea, vomiting, mucositis, fatigue and pain: parameter estimates (ß), standard error (SE), 95% confidence interval (CI) and p values based on GEE analyses
Predictor variable | Nausea | | Vomiting |
ß | SE | 95% CI | P value | | ß | SE | 95% CI | P value |
Intercept | 11.10 | 3.44 | 4.34–17.85 | 0.001 | | 3.24 | 2.17 | -1.01-7.50 | 0.136 |
Intervention groupa | -5.47 | 4.93 | -15.13-4.19 | 0.267 | | 0.15 | 1.89 | -3.55-3.86 | 0.936 |
Cycle 1b | 9.47 | 3.81 | 2.01–16.93 | 0.013 | | 2.23 | 2.63 | -2.92-7.37 | 0.397 |
Cycle 2 b | 12.89 | 4.42 | 4.22–21.57 | 0.004 | | -1.17 | 2.24 | -5.56-3.22 | 0.600 |
Cycle 3 b | 11.88 | 4.63 | 2.81–20.96 | 0.010 | | 0.39 | 3.22 | -5.92-6.70 | 0.904 |
Cycle 4 b | 5.66 | 4.11 | -2.39-13.71 | 0.168 | | -3.04 | 1.70 | -6.37-0.30 | 0.074 |
Cycle 5 b | 6.82 | 4.18 | -1.36-15.01 | 0.102 | | -3.02 | 1.70 | -6.35-0.31 | 0.075 |
Treatment modificationc | 0.55 | 4.73 | -8.71-9.82 | 0.907 | | -1.71 | 0.88 | -3.44-0.02 | 0.053 |
Predictor variable | Mucositis | | Fatigue |
ß | SE | 95% CI | P value | | ß | SE | 95% CI | P value |
Intercept | 3.03 | 2.62 | -2.11-8.17 | 0.248 | | 29.70 | 5.18 | 19.53–39.83 | < 0.001 |
Intervention groupa | -3.06 | 3.78 | -10.47-4.36 | 0.419 | | 2.42 | 5.71 | -8.77-13.62 | 0.671 |
Cycle 1b | 15.30 | 3.96 | 7.53–23.07 | < 0.001 | | 5.12 | 3.45 | -1.66-11.87 | 0.139 |
Cycle 2 b | 11.27 | 2.98 | 5.43–17.12 | < 0.001 | | 7.20 | 3.92 | -0.50-14.89 | 0.067 |
Cycle 3 b | 13.41 | 4.03 | 5.51–21.31 | 0.001 | | 7.37 | 5.38 | -3.17-17.90 | 0.171 |
Cycle 4 b | 10.57 | 3.47 | 3.77–17.37 | 0.002 | | 6.34 | 4.55 | -2.57-15.25 | 0.163 |
Cycle 5 b | 10.94 | 3.59 | 3.90-17.98 | 0.002 | | 8.11 | 5.38 | -2.43-18.65 | 0.132 |
Treatment modificationc | -6.13 | 4.22 | -14.42-2.14 | 0.146 | | 12.28 | 6.62 | -0.71-25.26 | 0.064 |
Predictor variable | Pain |
ß | SE | 95% CI | P value |
Intercept | 30.13 | 4.76 | 20.80-39.47 | < 0.001 |
Intervention groupa | 2.19 | 5.69 | -8.95-13.34 | 0.700 |
Cycle 1b | -2.45 | 4.00 | -10.29-5.39 | 0.540 |
Cycle 2 b | -3.07 | 4.69 | -12.26-6.11 | 0.512 |
Cycle 3 b | -1.77 | 5.48 | -12.50-8.97 | 0.747 |
Cycle 4 b | -0.31 | 5.27 | -10.63-10.01 | 0.953 |
Cycle 5 b | -1.98 | 4.36 | -10.51-6.56 | 0.650 |
Treatment modificationc | -6.58 | 5.57 | -17.50-4.35 | 0.238 |
aReference group: control group; bReference group: Cycle 0; cReference group: no |
Non-significant reductions of symptom burden in the intervention group were estimated for nausea and mucositis. Treatment modification, i.e. dose reduction, therapy interruption, change of therapy, or discontinuation of therapy, led to lower estimates of symptom burden for vomiting, mucositis, and pain. There might have been interaction effects between therapy cycle and treatment modification, which however, could not be analyzed in our GEE models due to the relatively small sample size.
Health-related quality of life
Health-related quality of life is shown per cycle and group in Suppl. 6. We observed a large variability of health-related quality of life among patients. However, the differences between the two groups were small and not significant at any treatment cycle.