Cancer Pain Management: Challenges and Progress in Pharmaceutical Development

The pharmaceutical industry faces ongoing challenges in developing effective treatments for cancer-related pain, even as patients live longer with the disease. Despite advances in cancer therapies, pain management options have not kept pace, leaving millions suffering from debilitating symptoms.

The Scope of Cancer Pain

Cancer pain affects between 20% to 50% of patients, with estimates rising to 80% for those with advanced disease. As improved treatments extend survival times, more patients are living with chronic pain for longer periods. The pain can manifest in diverse ways - from tumors compressing nerves and organs to treatment side effects like chemotherapy-induced neuropathy.

Mary Sage, diagnosed with multiple myeloma in 2015, describes her pain as "sharp, energetic, searing, as if electricity was ricocheting from her hips to her neck." She takes 32 pills daily, including opioids, to manage her symptoms. Michael Tuohy, another myeloma survivor, experienced excruciating pain after a surgery to reinforce his cancer-damaged spine, requiring high doses of opioids for over a decade.

Limitations of Current Treatments

Opioids remain the cornerstone of cancer pain management, despite their risks of addiction and side effects. "Cancer pain is a whole different ball game," says Allyson Beechy, a clinical pharmacy specialist at Dana Farber Cancer Institute. "It's the most severe pain I've ever seen, and very stubborn."

However, prolonged opioid use can lead to tolerance, hyperalgesia, and withdrawal symptoms. Patients like Sage describe tapering off opioids as a "nightmarish" process. Additionally, supply constraints and insurance barriers often limit access to needed medications.

Non-opioid alternatives have shown limited efficacy for severe cancer pain. Vertex Pharmaceuticals' recently approved sodium channel blocker Journavx, while promising for acute pain, is not expected to be useful for the persistent pain cancer causes.

Challenges in Drug Development

Despite the clear need, pharmaceutical companies have largely shied away from pain research. Steven Paul, a neuroscientist and biotech entrepreneur, explains: "The challenge from a commercial perspective is finding something so unequivocally better than a cheap opiate or a cheap nonsteroidal. You're going to have to beat those babies."

The complex biology of pain and high failure rates in clinical trials make it a risky investment. Most ongoing research focuses on more common conditions like post-surgical or diabetic nerve pain rather than cancer-specific pain mechanisms.

Emerging Research and Future Directions

Despite the obstacles, some progress is being made. The National Institutes of Health recently reported promising early trial results for a new therapy derived from a cactus-like plant for intractable cancer pain. Researchers at Harvard and Virginia Commonwealth University have shed new light on the genetics of nerve-infiltrating tumors and chemotherapy-induced neuropathy.

Smaller biotechs like Tris Pharma and Rapport Therapeutics are working on novel pain medications, though their potential application to cancer pain remains uncertain. As Steven Paul notes, "We have better tools, better targets, better biology, but it's still somewhat early days."

For now, cancer centers are experimenting with multi-modal approaches, combining pain pumps, nerve blocks, and both opioid and non-opioid medicines. However, as Dana Farber's Beechy observes, "I feel like we almost need a whole new category. But I have no idea how anyone would find that."