minocycline and Colorectal-Neoplasms

The most debilitating symptoms during oxaliplatin-based chemotherapy in patients with colorectal cancer (CRC) are neuropathy and fatigue. Inflammation has been suggested to contribute to these symptoms, and the anti-inflammatory agent minocycline is safe and readily available.. This proof-of-concept study investigated minocycline's capacity to reduce treatment-related neuropathy and fatigue and its impact on inflammatory markers during chemotherapy in a Phase II randomized, double-blind, placebo-controlled clinical trial.. Patients with locally advanced or metastatic CRC who were scheduled for oxaliplatin-based chemotherapy were randomly assigned to receive either minocycline (100 mg twice daily) or placebo over four months from started chemotherapy. Toxicity assessments and blood samples were prospectively collected monthly. The severity of fatigue and numbness/tingling was assessed weekly using the MD Anderson Symptom Inventory. The primary endpoint, area under the curve for numbness/tingling and fatigue over approximately four months, was compared between the two arms.. Of 66 evaluable participants, 32 received minocycline and 34 placebo. There was no observed significant symptom reduction on both fatigue and numbness/tingling in either arm, nor was there a difference in levels of serum proinflammatory and anti-inflammatory markers between arms. No Grade 3 adverse events nor disparity mediating effects on intervention were observed.. Minocycline treatment is feasible and has a low-toxicity profile. However, with 200 mg/day, it did not reduce numbness/tingling or fatigue nor moderate inflammatory biomarkers from this Phase II randomized study. Our results do not support further exploration of minocycline for fatigue or neuropathy symptom intervention in patients treated for CRC.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Colorectal Neoplasms; Double-Blind Method; Fatigue; Female; Humans; Male; Middle Aged; Minocycline; Oxaliplatin; Peripheral Nervous System Diseases; Proof of Concept Study; Prospective Studies; Symptom Assessment

To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy.. Metastatic colorectal cancer patients preparing to initiate cetuximab were randomly assigned to receive daily oral minocycline or placebo, and to receive topical tazarotene application to either left or right side of the face. Both therapies were administered for 8 weeks.. Forty-eight eligible patients were randomly assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4. At week 4, a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial photographs, obtained at week 4, were reviewed for rash global severity. Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo (20% v 42%, P = .13). The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8. Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm, and none in the minocycline arm. There was no observed clinical benefit to tazarotene application. Tazarotene treatment was associated with significant irritation, causing its discontinuation in one third of patients.. Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment. Topical tazarotene is not recommended for management of cetuximab-related rash.

Topics: Acneiform Eruptions; Administration, Oral; Administration, Topical; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; Colorectal Neoplasms; Dermatologic Agents; Double-Blind Method; ErbB Receptors; Female; Humans; Male; Middle Aged; Minocycline; Nicotinic Acids; Placebos

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Metastasis is a major cause of CRC recurrence and mortality. Several antibiotic drugs have been reported to exert potential anticancer activities, however, whether and how the tetracycline antibiotic minocycline exhibit tumor suppressive effect on CRC remains unknown. Here, we found that minocycline markedly inhibits the epithelial-mesenchymal transition (EMT) process and metastasis of CRC cells both

Topics: Anti-Bacterial Agents; Cell Line, Tumor; Cell Movement; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Minocycline; Neoplasm Metastasis; STAT3 Transcription Factor

Cancer drug treatment is often discontinued because of skin disorder aggravation. However, information on risk factors for skin disorders caused by anti-epidermal growth factor receptor (EGFR) antibody drugs is limited. The aim of this study was to analyse the factors associated with skin disorders caused by anti-EGFR antibody drugs and establish a method to minimize such aggravations.. We retrospectively examined 67 colorectal cancer patients treated with anti-EGFR antibody drugs for the first time.. A higher proportion of males than females experienced drug withdrawal, dose reduction or treatment discontinuation. The multiple logistic regression analysis revealed body weight as a risk factor affecting drug withdrawal, dose reduction or treatment discontinuation because of an acneiform rash. An examination of methods to avoid the aggravation of skin disorders revealed the acneiform rash grade in patients who received prophylactic minocycline was significantly lower than that in patients who did not receive prophylactic minocycline. Furthermore, among patients with grade 1 acneiform rash at the initiation of minocycline, the proportion of those who withdrew, required dose reduction or discontinued treatment was lower than that among patients with grade 2 acneiform rash.. High body weight was identified as a novel factor for skin disorder aggravation caused by anti-EGFR antibody drugs. The aggravation of skin disorders during cancer treatment with anti-EGFR antibody drugs can potentially be avoided by carefully observing the onset of acneiform rash in affected patients with high body weight and using minocycline prophylactically or as an early-stage intervention.

Topics: Age Factors; Aged; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Colorectal Neoplasms; ErbB Receptors; Female; Humans; Logistic Models; Male; Middle Aged; Minocycline; Patient Dropouts; Quality of Life; Retrospective Studies; Sex Factors; Skin Diseases

Although the anti-EGFR monoclonal antibody panitumumab is effective in treating colorectal cancer, the occurrence of severe skin disorders often discontinues therapy. Herein, we investigated by a retrospective chart review the effect of prophylactic oral minocycline in combination with skin treatment using moisturizer on the incidence of skin disorders and tumor response in metastatic colorectal cancer patients who received panitumumab.. In a total of 55 patients, 38 patients were eligible, consisting the pre-emptive group (N=25) and reactive group (N=13). Acneiform rash and other adverse events were graded according to the CTCAE v4.0.. The occurrence of acneiform rash (grade ≥2) was significantly lower in pre-emptive group than in reactive group (44.0% vs. 84.6%, p=0.04). No significant differences in the occurrence of other adverse events were observed between the two groups. Tumor response was not significantly different between the two groups (36.0% vs. 7.7%, OR, 6.75; 95% confidence interval (CI)=0.75-60.76, p=0.12). Mean time to treatment failure was 149.7 days and 110.2 days in the pre-emptive group and reactive treatment group, respectively (HR=0.58; 95% CI= 0.26-1.28, p=0.18).. Prophylactic oral minocycline combined with skin care reduced panitumumab-induced acneiform rash without a significant influence on tumor response.

Topics: Acneiform Eruptions; Administration, Oral; Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibodies, Monoclonal; Antineoplastic Agents; Cohort Studies; Colorectal Neoplasms; Drug Therapy, Combination; Exanthema; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Minocycline; Neoplasm Staging; Panitumumab; Prognosis; Skin Care