Long-term neuropathy and quality of life in colorectal cancer patients treated with oxaliplatin containing adjuvant chemotherapy

Abstract

Background: Oxaliplatin, combined with capecitabine (CAPOX) or infused 5-fluorouracil (FOLFOX), is standard of care in the adjuvant treatment of colorectal cancer (CRC). Prospective data on prevalence of oxaliplatin induced acute and long-term neuropathy in a real-life patient population and its effects on quality of life (QOL) and survival is limited, and scarce in CAPOX versus FOLFOX treated, especially in a subarctic climate. Methods: One hundred forty-four adjuvant CRC patients (all 72 CAPOX cases and 72 matched FOLFOX controls) were analyzed regarding oxaliplatin induced sensory neuropathy, which was graded according to NCI-CTCAEv3.0. Ninety-two long-term survivors responded to the QOL (EORTC QLQ-C30) and Chemotherapy-Induced Peripheral Neuropathy (EORTC CIPN20) questionnaires and were interviewed regarding long-term neuropathy. Results: Acute neurotoxicity was present in 94% (136/144) during adjuvant therapy and there was a significant association between acute neurotoxicity and long-term neuropathy (p < .001). Long-term neuropathy was present in 69% (grade 1/2/3/4 in 36/24/8/1%) at median 4.2 years. Neuropathy grades 2-4 did not influence global health status, but it was associated with decreased physical functioning (p ¼ .031), decreased role functioning (p ¼ .040), and more diarrhea (p ¼ .021) in QLQ-C30 items. There were no differences in acute neurotoxicity, long-term neuropathy, or in QOL between CAPOX and FOLFOX treated. Neuropathy showed no pattern of variation according to starting and stopping month or treatment during winter. Conclusions: Neuropathy following oxaliplatin containing adjuvant chemotherapy is present in twothirds, years after cessation, and impairs some QOL scales. There is no difference in severity of acute or long-term neuropathy between CAPOX and FOLFOX treated and QOL is similar. No seasonal variation in neuropathy was noted.

High symptom burden is associated with impaired quality of life in colorectal cancer patients during chemotherapy:A prospective longitudinal study

“…Numbness/tingling worsened over time (in patients receiving oxaliplatin) and was associated with impaired physical QoL in Paper III. This is consistent with previous reports on a cumulative increase in severity in numbness/tingling [208] in the feet over time for 1 year after enrolment. [154] In the latter study, numbness/tingling in the hands peaked after 3 months of treatment and decreased by 1 year after enrolment.…”

“…[218] Given the lack of effective treatment for numbness/tingling, it is important to assess this symptom and its severity systematically and to modify the chemotherapy dose when needed (dose limitation). [208,219]…”

Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer

“…Even if the magnitude of the chronic problems described in the pivotal adjuvant trials was limited, many clinicians still experienced this to be an outstanding issue, in line with the report by Soveri et al [9], and at least five different randomized trials comparing a shorter oxaliplatin treatment (3 months) with the standard 6 months of treatment were initiated to show that 3 months did not give inferior results but less OIPN. The rapid inclusion of together well over 10,000 patients [10] clearly tells that both doctors and the patients they informed about the trials considered this research question well worth exploring and participating in.…”

“…In one of the trials comparing 3 vs 6 months of adjuvant FOLFOX or CAPOX, the SCOT trial [11], another patientreported outcome measure than CIPN20, used by Soveri et al [9], the FACT/GOG NTx-4 scale was used. The scores in the 6-month arm (approximately 60% of patients actually received 6 months oxaliplatin) were about twice as high as in the 3-month arm (approximately 85% received 3 months), showing that longer treatment gives more acute and late neurotoxicity.…”

“…The results of retrospective, sometimes cross-sectional studies have been reported through the years, describing clearly more problems than reported from the pivotal clinical trials [7,8]. In this issue of Acta Oncologica, Soveri et al [9] present the results from a prospective study including 144 Finnish patients with CRC (85% stage III) receiving adjuvant CAPOX (n ¼ 72) or a modified FOLFOX6 regimen (n ¼ 72 matched controls). Ninety-two long-term survivors (median follow-up 4.2 years) responded to the general quality of life (QoL) instrument EORTC-QLQ-C30 and to one of a few frequently used instruments evaluating chemotherapyinduced peripheral neuropathy (CIPN), EORTC-CIPN20.…”