Cis vs MMC in Anal Cancer - The Right way, the wrong way, and the MDA way

[medgator]

Plus, there's the (phase III data-free) "MDA way" they all practice, which can clash with other institutions.

Simul mentioned not using MMC in anal scc as one

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[Mandelin Rain]

Simul mentioned not using MMC in anal scc as one

That was always so unusual to me. Being dogmatic about cis vs mmc in the face of data showing it's worse. Just a bizarre hill to die on.

 

[evilbooyaa]

That was always so unusual to me. Being dogmatic about cis vs mmc in the face of data showing it's worse. Just a bizarre hill to die on.

Eh. MMC is more toxic ( "although more patients had grade 3 haematological toxic effects in the mitomycin group than in the cisplatin group (26% vs 16%; p<0·001)." ).

Cis in ACT-II when not futzing about with induction (which was the main issue IMO of 9811 and ACCORD-03, not the fact that it's Cis) seems reasonable. ACT-II liked MMC b/c it wasn't a non-inferiority trial, but it's a one-time thing that didn't require hydration resources of cis, which UK-based NHS loves (less having to be done for patients).

I have zero problems with an institutional policy being "Cis for all" in anal SCC.

If you'd like to discuss further, let me know and I'll turn it into it's own thread to avoid de-railing further.

 

[RickyScott]

Eh. MMC is more toxic ( "although more patients had grade 3 haematological toxic effects in the mitomycin group than in the cisplatin group (26% vs 16%; p<0·001)." ).

Cis in ACT-II when not futzing about with induction (which was the main issue IMO of 9811 and ACCORD-03, not the fact that it's Cis) seems reasonable. ACT-II liked MMC b/c it wasn't a non-inferiority trial, but it's a one-time thing that didn't require hydration resources of cis, which UK-based NHS loves (less having to be done for patients).

I have zero problems with an institutional policy being "Cis for all" in anal SCC.

If you'd like to discuss further, let me know and I'll turn it into it's own thread to avoid de-railing further.

Spoke to Chris crane about this a number of years ago and came away convinced that cis was very reasonable.

 

[Mandelin Rain]

I don't think much is unreasonable. Cis in anal cancer is not one of those things. I don't care. It just always seemed strange to me to keep fighting and fighting that battle. Like altered fractionation in H/N in chemo era or pelvic nodes for prostate cancer. It's reasonable to do a lot of stuff. No need to rehash it again and again.

On orals CC was my GI examiner (probably one of my favorite examiners. He was teaching me new stuff while examining me, like you can't help but learn while you're around him), and I answered MMC for anal ca knowing he may object and obviously in a bad spot to defend myself vs him. No sigh. No groan. No raised eyebrow. We just moved on.

 

[Neuronix]

If you look at ACT-II, cis and MMC were equivalent Mitomycin or Cisplatin Chemoradiation With or Without Maintenance Chemotherapy for Treatment of Squamous-Cell Carcinoma of the Anus (ACT II): A Randomised, Phase 3, Open-Label, 2 × 2 Factorial Trial - PubMed

The conclusion of the abstract states " The results of our trial—the largest in anal cancer to date—show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK."

But why? If cisplatin is equivalent, why insist on MMC especially when there's more heme toxicity? Shrug.

 

[Mandelin Rain]

Best reason is... ACT II was published after I took Orals but 9811 was widely available and known.

EDIT: Additionally, I think ACT II was not designed as a non-inferiority or equivalence trial, though I could be wrong.

EDIT 2: It was a superiority trial for Cis (not sure why, but that was the design). Cis failed to show superiority, so it lost. In America, despite losing, it would become the standard arm of the follow up trial (cough *RTOG 0129* cough), but in the MRC, I guess that doesn't fly.

 

[evilbooyaa]

If you look at ACT-II, cis and MMC were equivalent Mitomycin or Cisplatin Chemoradiation With or Without Maintenance Chemotherapy for Treatment of Squamous-Cell Carcinoma of the Anus (ACT II): A Randomised, Phase 3, Open-Label, 2 × 2 Factorial Trial - PubMed

The conclusion of the abstract states " The results of our trial—the largest in anal cancer to date—show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK."

But why? If cisplatin is equivalent, why insist on MMC especially when there's more heme toxicity? Shrug.

Was a superiority trial, not non-inferiority. Authors are obliged to conclude that if a regimen is not superior than the control arm remain SOC.

Similar to CONVERT trial, where 66/33 was supposed to be superior to Turrisi. It wasn't, so conclusion (appropriately) says Turrisi is 'SOC'.

Anyways, going to pull this into it's own thread given the discussion.

 

[Ray D. Ayshun]

I thought this was answered as well: we give 28-30 treatments, minimizing breaks. Some of those days they might be late bc they're getting chemo.

 

[Reaganite]

Spoke to Chris crane about this a number of years ago and came away convinced that cis was very reasonable.

That man's mednet write ups alone should be required reading for every rad onc resident. Bar none my favorite academic out there. If he's pushing for cis, I gotta reevaluate lol.

 

[elementaryschooleconomics]

That man's mednet write ups alone should be required reading for every rad onc resident. Bar none my favorite academic out there. If he's pushing for cis, I gotta reevaluate lol.

Strongly agree. Can we get him on this new Virtual Visiting Professor thing?

 

[Burt Radnolds]

If you look at ACT-II, cis and MMC were equivalent Mitomycin or Cisplatin Chemoradiation With or Without Maintenance Chemotherapy for Treatment of Squamous-Cell Carcinoma of the Anus (ACT II): A Randomised, Phase 3, Open-Label, 2 × 2 Factorial Trial - PubMed

The conclusion of the abstract states " The results of our trial—the largest in anal cancer to date—show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK."

But why? If cisplatin is equivalent, why insist on MMC especially when there's more heme toxicity? Shrug.

The real answer I'm told, and this is not a dig, is socialized medicine. This study was done in the UK. The decreased resource utilization of mmc with a quick infusion outweighs the decreased toxicity of cis and it's prolonged infusion.

 

[evilbooyaa]

That man's mednet write ups alone should be required reading for every rad onc resident. Bar none my favorite academic out there. If he's pushing for cis, I gotta reevaluate lol.

Agreed. Don't agree with 100% of his writings but darn near most of them.

My favorite line of his - Time to generate some data.

 

[ramsesthenice]

The real answer I'm told, and this is not a dig, is socialized medicine. This study was done in the UK. The decreased resource utilization of mmc with a quick infusion outweighs the decreased toxicity of cis and it's prolonged infusion.

Bingo. They spell it out right in the discussion section of the paper. "Although grade 3–4 haematological toxic effects were less common with fluorouracil plus cisplatin (26% vs 16%) patients, these were almost entirely related to white blood cells but were not sufficient to increase neutropenic sepsis. This marginal benefit is likely to be outweighed by the extra resources needed to administer cisplatin—two courses of either all day or overnight intravenous treatment with hydration, compared with only a single dose of mitomycin delivered over 10 min."