By Carol Humphry, M.D., Family Medicine Department, Kamuzu University of Health Sciences, Mangochi District Hospital, Mangochi, Malawi

In July of 2020 Mangochi District Hospital began administering paclitaxel for Kaposi's sarcoma (KS) patients. From the initiation of the programme until the end of September 2022, we treated 145 men and 51 women. 

There have been remarkable responses with shrinking tumours and improved quality of life for many people. Working in a low or middle-income country (LMIC) poses some challenges that require chemotherapy administration without entirely adhering to best practices.  

However, the benefits for so many people have encouraged us to continue with this medication as we are able. Unfortunately, we have no more paclitaxel at this time and patients are going without treatment.  

When we first started, patients had been receiving vincristine and bleomycin as their chemotherapy for Kaposi's sarcoma. This combination works about 44% of the time while paclitaxel works 64% of the time¹.  

One of our early patients returned for his second or third paclitaxel cycle and enthusiastically told us “I tell my friends this is a miracle drug.”  

Another man who had a large tumour around his ankle, came back with the mass looking about the same after two or three cycles. However, he was thrilled to report he had been able to return to riding a bicycle (our community has numerous men who earn their living as bicycle taxi drivers). 

Many patients with lower extremity tumours have remarked that they can walk again or wear shoes when they had not been able to do so for months prior to starting paclitaxel. This means they can gather firewood, haul water, manage household chores, work to support their families, etc. 

The benefits of paclitaxel for some people have been so tremendous that we continued its administration under less-than-ideal circumstances.  

Discussion

Preferably, all cancers would be diagnosed through examination of biopsies.  That is usually not possible in our LMIC setting.  For our patients, it can be more than the equivalent of $30.00 US dollars (USD) to get a specimen to a pathology lab and obtain a result.    

There is a $13.00 option, but it involves waiting a month for the answer and running the risk that the result is lost in the meantime.  The vast majority of our patients cannot afford either choice. For many, the average income may be as low as $100 to $200 USD per year². 

Thus we diagnose most people through clinical suspicion and favourable response to our chemotherapy. 

While standard of care requires close monitoring of FBC or CBC (Full or Complete Blood Count) and LFTs (Liver Function Tests) prior to drug administration, and withholding or adjusting the dose accordingly, we have occasions where such laboratory tests are simply not available.   

Some patients spend a chunk of their limited income on transportation (like 5 to 10 USD) to and from the hospital. We have felt that denying them the wonderful benefits they get with paclitaxel, because our laboratory on that particular day is unable to perform the necessary blood tests, is cruel.  

So we do, periodically, give this chemotherapy without proper monitoring ahead of time.  It is a risk.  Whenever asked, patients always request to proceed without the laboratory results. Of the 196 patients enrolled in our paclitaxel programme between July 2020 and September 2022, 104 were lost to follow-up. 

Some of those have stopped coming due to resolution of symptoms. Another 15 were known to have died. Of those that did not return, some are presumed to have passed on. 

Eighteen patients included in the lost-to-follow-up group, did not return for cycle #2, making one wonder if they were so sick that chemotherapy could not postpone their demise. 

On the other hand, numerous patients who suffered from pulmonary KS and struggled to breath or walk, experienced markedly improved function even after just one or two cycles.   

Other patients lost to follow-up have returned to our care months later (and get removed from the list of missing people), often stating that they could not source the funds to pay for transportation.   

Some patients come back just a few weeks later than expected, thus disrupting their cycle schedule and presumably the efficacy of their chemotherapy. 

It is frustrating that we have had this expensive and helpful medication, but cannot give it in a timely fashion to all the people who need it. In our low-resource setting (a LMIC), clinicians, nurses and space are limited. This means corners may get cut in administering paclitaxel. 

For instance, usual practice is to give dexamethasone twelve and six hours prior to giving the chemotherapy.   

The Malawi Clinical HIV Guidelines advise the steroid be given with the other pre-drugs (paracetamol/acetaminophen and chlorphenamine) only once, 30 to 60 minutes before paclitaxel³.  Such an abbreviated dexamethasone protocol has been studied previously⁴ and it has worked well for us in Mangochi. In two plus years, we had only one patient, on his second cycle, with anaphylaxis.  This brought up another limitation in our setting. 

In this particular case, it was only because student nurses happened to be on the ward that this man's adverse reaction was caught and dealt with in a timely and appropriate manner.  

We just do not have the nursing staff to be able to closely observe patients as much as preferred during IV infusions, and we have to depend on notification from patients and their family members to help us address complications.

Clinicians experienced in the administration of paclitaxel may have noted the pre-drugs advised by the Malawi Guidelines, referenced above, do not include the best-practice use of cimetidine or famotidine. 

Neither of these drugs has been available in Malawi since ranitadine was removed from the market. We have had to make other substitutions, such as prednisolone rather than dexamethasone, due to availability of certain medications in our hospital. 

Finally, due to overwhelming numbers of other patients needing our attention, clinicians have, on rare occasions, administered a lower or higher dose of the chemotherapy than recommended. 

Of course this can happen in any setting. But the few times where it has been noted here, it occurred mostly due to busy providers doing too many tasks at once.  
 

Next Steps

Our experience supports the development of oncology treatment in a district hospital. The therapy has benefited patients with improved quality of life and longevity. 

The greatest challenge is to address the multiple factors that consume resources and provide little value as evident by the significant number of patients lost to follow-up or not receiving treatment based on protocol. The future programme needs to focus on community support factors.

Procurement of the paclitaxel and the associated medication required by the protocol: paclitaxel requires repeated 3 week cycles of the chemotherapy. 

Establishing a stable supply of medication would result in many more patients benefiting from the programme. Transportation for patients is a critical factor in chronic management of Kaposi's sarcoma.

The cost of a cycle of paclitaxel is about $1000 USD in that nation. It does not make sense to initiate chemotherapy, only to have it fail because the patient does not have $10 to come for care. 

There is no easy solution as the pot of money for medication and treatment does not include paying for transportation. 

There may need to be creative solutions to address patients' commute for the programme to be more effective than it is at present.  

Patient education and staff training is an ongoing process. This needs to include addressing the barriers to regular transportation and the cultural issues related to a long-term commitment to therapy.

Conclusion

It is exceedingly rewarding, as a clinician, to give paclitaxel to patients with Kaposi's sarcoma and watch as their quality of life improves.  

Having it available in a district hospital, as opposed to needing to travel three hours to the central hospital in the city, has vastly improved access to treatment for many cancer patients. 

Not everyone does well and not everyone survives, but overall this chemotherapy has been incredibly well received and appreciated.  It was even suggested that an honorary Chief-of-a-Village title be given to this physician.  

The tragedy, of course, is that our drug supply is not reliable and patients, when they do make it to the hospital, are unable to access chemotherapy as much as needed. 

As of the writing of this paper, not only are we completely out of paclitaxel, but we do not even have the vincristine to offer in its place.

References

1.  Krown SE, Moser CB, MacPhail P, Matining RM, Godfry C, Caruso SR, Hosseinipour MC, Wadzanai S, Nyirenda M, Busakhala NW, Okuku FM, Kosgei J, Hoagland B, Mwelase N, Oliver VO, Burger H, Mngqibisa R, Nokta M, Campbell TB and Borok MZ  (2020)  Treatment of Advanced AIDS-Associated Kaposi's Sarcoma in Resource-Limited Settings:  a three-arm, open-label randomised, non-inferiority trial   The Lancet  395 (10231):  1195 - 207

2.  Ripple Africa. Date accessed: 24/04/23

3.  (2022)  Malawi Guidelines for Clinical Management of HIV in Children and Adults:  30

4.  Bookman MA, Kloth DD, Kour PE, Smolinski S and Ozols RF (1997)  Short-Course Intravenous Prophylaxis for Paclitaxel-Related Hypersensitivity Reactions  Annals of Oncology 8 (6):  611- 4  

Read an Editorial "The Reality of Cancer Care for Many - Richard Sullivan and Eduardo Cazap", published in ecancermedicalscience on this topic here