What is the best approach to manage pancreatic cancer in a patient with Human Immunodeficiency Virus (HIV) infection?

Management of Pancreatic Cancer in Patients with HIV

Patients with HIV and pancreatic cancer should receive the same standard cancer treatment as HIV-negative patients, with HIV status alone never serving as a criterion to withhold or modify cancer therapy. 1

Core Treatment Principle

HIV-positive patients must receive full-dose, guideline-concordant pancreatic cancer treatment identical to HIV-negative patients, while maintaining antiretroviral therapy (ART) throughout cancer treatment with careful attention to drug-drug interactions. 1, 2

• The NCCN explicitly states that HIV status alone should not be used for cancer treatment decision-making 1
• Appropriate cancer treatment can be successfully delivered when oncologists and HIV specialists work together to optimize care for both diseases 1
• ART should be initiated and/or continued during cancer therapy to reduce infectious complications and improve HIV control 1

Mandatory Multidisciplinary Approach

All patients require co-management by an HIV specialist, oncologist, HIV pharmacist, and oncology pharmacist before initiating any cancer treatment. 2

• This collaboration is essential because 45% of oncologists rarely or never discuss management plans with HIV specialists, contributing to suboptimal care 1
• All proposed therapies must be reviewed for drug-drug interactions and overlapping toxicities prior to initiation 2

Antiretroviral Therapy Management During Cancer Treatment

Preferred ART Modifications

Switch to integrase inhibitor-based ART regimens without ritonavir or cobicistat boosters as the preferred strategy during pancreatic cancer treatment. 2

• Integrase inhibitors have the lowest potential for drug-drug interactions with chemotherapy agents 2
• ART interruptions should be avoided due to risk of immunologic compromise, opportunistic infection, and death 2

Antiretrovirals to Absolutely Avoid

The following antiretrovirals are contraindicated or require avoidance during pancreatic cancer chemotherapy:

• Zidovudine is absolutely contraindicated when myelosuppressive chemotherapy is planned 2
• Ritonavir, cobicistat, and protease inhibitors must be avoided due to CYP3A/4 inhibition causing dangerous interactions with most chemotherapy agents 2
• Didanosine and stavudine must be avoided due to additive peripheral neuropathy with chemotherapy agents 2
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be used with caution as they induce CYP3A/4, potentially decreasing chemotherapy efficacy 2

Timing of ART Initiation or Modification

Initiate or modify ART either ≥7 days prior to cancer treatment OR after cancer therapy tolerance is established to separately assess tolerability. 2

• ART should be offered immediately if not already receiving it, but adapted according to the cancer treatment plan 2

Pancreatic Cancer Treatment by Stage

Resectable Disease

Surgical resection should be performed at specialist centers with pancreaticoduodenectomy as the standard procedure, followed by adjuvant chemotherapy with either gemcitabine or 5-FU/folinic acid. 1

• HIV status alone should not be a criterion for decision-making regarding surgical interventions 1
• Recent data demonstrate that clinical outcomes, length of stay, and complications are similar between HIV-positive and HIV-negative patients for most surgical procedures 1
• Overall health (organ dysfunction, nutritional state) is a more reliable predictor of surgical outcome than CD4+ T-cell counts or HIV viral loads 1
• Standard lymphadenectomy should involve removal of ≥15 lymph nodes for adequate pathologic staging 1

Borderline Resectable Disease

Administer chemotherapy followed by chemoradiation, then surgery if the patient is not enrolled in a clinical trial. 1

• Patients with borderline resectable lesions should be included in clinical trials wherever possible 1

Locally Advanced Unresectable Disease

The standard of care is 6 months of gemcitabine monotherapy. 1

• Chemoradiation has a minor role in this subgroup, with classical capecitabine plus radiotherapy being the only recommended combination if chemoradiation is pursued 1

Metastatic Disease

For patients with ECOG performance status 0-1 and bilirubin <1.5× ULN, use either FOLFIRINOX or gemcitabine plus nab-paclitaxel combination chemotherapy. 1

• For performance status 2 and/or bilirubin >1.5× ULN, consider gemcitabine monotherapy 1
• For performance status 3-4 with significant morbidities and very short life expectancy, only symptomatic treatment should be considered 1
• In very selected patients with ECOG performance status 2 due to heavy tumor load, gemcitabine and nab-paclitaxel can be considered for best chance of response 1

Palliative Care Considerations

Biliary Obstruction Management

Endoscopic stent placement is preferable to trans-hepatic stenting or surgical bypass for most patients requiring relief of obstructive jaundice. 1, 3

• Metal stents have lower risk of recurrent bile duct obstruction (RR 0.52; 95% CI 0.39-0.69) compared to plastic stents 3
• For patients with life expectancy >6 months, surgical bypass may be preferred over stenting 1, 3
• For patients with life expectancy >3 months, metal stents are preferred over plastic stents due to longer patency duration (median 3.6 months vs 1.8 months) 3

Gastric Outlet Obstruction

For symptomatic gastric outlet obstruction, use endoscopic stenting for patients with poor performance status or limited life expectancy, and laparoscopic gastrojejunostomy for those with good performance status and life expectancy >3-6 months. 3

• Prophylactic gastrojejunostomy is recommended during surgical bypass for unresectable tumors, as approximately 20% of patients will develop late gastric outlet obstruction requiring intervention 3

Supportive Care and Infection Prophylaxis

Enhanced Monitoring Requirements

Implement more frequent HIV viral load testing (monthly for first 3 months, then every 3 months) due to potential ART-chemotherapy interactions. 2

• CD4+ T-cell counts should be measured more frequently in patients receiving lymphopenia-inducing treatments 2

Opportunistic Infection Prophylaxis

Initiate Pneumocystis jiroveci pneumonia (PCP) prophylaxis for all patients with CD4 counts <200 cells/μL. 1, 2

• Consider PCP prophylaxis even with higher CD4 counts due to expected decline during chemotherapy 2
• Follow standard opportunistic infection prophylaxis guidelines based on CD4+ count 2
• For profound immunosuppression/myelosuppression, myeloid growth factor support is required 1
• Consider antifungal prophylaxis in appropriate cases 1

Antiemetic Therapy Modifications

Limit general use of steroids for antiemesis in HIV-positive patients because steroids may increase risk of opportunistic infections. 1

• However, steroids can be used briefly as premedication for or following chemotherapy when cancer treatment involves agents associated with delayed nausea/vomiting 1

Mucosal Toxicity Management

Maintain high index of suspicion for opportunistic infections including fungal and cytomegalovirus (CMV) when patients develop oral mucositis, esophagitis, or colitis. 1

• There is increased risk of mucosal toxicity secondary to mucosal sensitivity and opportunistic infections 1
• Early testing for opportunistic infections and consultation with infectious disease or HIV specialist is appropriate 1

Special Hepatitis B Co-infection Considerations

In patients co-infected with hepatitis B, select an ART regimen that treats both HIV and hepatitis B. 2

• This is particularly important as 26% of HIV-positive patients with pancreatitis may have markers for HBV, and 36% with CD4 <50 had persistent HBV in one study 4

Critical Pitfalls to Avoid

Never discontinue ART during cancer therapy unless absolutely necessary. 2

• ART interruptions lead to immunologic compromise, opportunistic infection risk, and increased mortality 2

Do not assume HIV patients require dose-reduced cancer therapy. 2

• HIV-positive patients should receive the same standard, full-dose cancer therapy used in the general population unless specific data exist for dose adjustments 2

Do not use HIV status as justification to withhold standard cancer treatment. 1

• 20-25% of oncologists stated they would not offer standard cancer therapy to people living with HIV, representing a critical care disparity 1

Avoid plastic stents if patient is likely to proceed to resection. 1

• Self-expanding metal stents should not be inserted in patients who are likely to proceed to resection 1

Prognosis Considerations

Pancreatic cancer in HIV-positive patients remains associated with severe prognosis at relatively young age (median 57 years), with median survival of 11 months after diagnosis. 5

• The incidence of pancreatic cancer in HIV-positive patients is estimated at 28 cases per 100,000 person-years 5
• 50% of patients have metastasis at diagnosis 5
• Most patients (91%) have suppressed HIV replication at pancreatic cancer diagnosis, indicating that well-controlled HIV does not prevent pancreatic cancer development 5